Gene Summary

Gene:MCM7; minichromosome maintenance complex component 7
Aliases: MCM2, CDC47, P85MCM, P1CDC47, PNAS146, PPP1R104, P1.1-MCM3
Summary:The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by the MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 4 and 6 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. Cyclin D1-dependent kinase, CDK4, is found to associate with this protein, and may regulate the binding of this protein with the tumorsuppressor protein RB1/RB. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]
Databases:VEGA, OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:DNA replication licensing factor MCM7
Source:NCBIAccessed: 15 March, 2017


What does this gene/protein do?
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Pathways:What pathways are this gene/protein implicaed in?
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Cancer Overview

Research Indicators

Publications Per Year (1992-2017)
Graph generated 15 March 2017 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Virus Replication
  • Signal Transduction
  • RT-PCR
  • Stomach Cancer
  • Immunohistochemistry
  • Viral Load
  • Cell Cycle Proteins
  • MicroRNAs
  • Pancreatic Cancer
  • Breast Cancer
  • Chromosome 7
  • Down-Regulation
  • Tissue Fixation
  • Translocation
  • Polycystic Ovary Syndrome
  • Cervical Cancer
  • Nuclear Proteins
  • Prostate Cancer
  • DNA Replication
  • Paraffin Embedding
  • Gene Expression Profiling
  • Liver Cancer
  • Trophoblastic Neoplasms
  • Proto-Oncogenes
  • Cell Proliferation
  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Thyroidectomy
  • Tissue Array Analysis
  • Protein-Serine-Threonine Kinases
  • Up-Regulation
  • Oligonucleotide Array Sequence Analysis
  • DNA-Binding Proteins
  • Tetradecanoylphorbol Acetate
  • Skin Cancer
  • Minichromosome Maintenance Complex Component 7
  • Transcriptional Activation
  • Young Adult
  • Transfection
  • Promoter Regions
  • Cancer Gene Expression Regulation
Tag cloud generated 15 March, 2017 using data from PubMed, MeSH and CancerIndex

Specific Cancers (8)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: MCM7 (cancer-related)

Lee JS, Cheong HS, Koh Y, et al.
MCM7 polymorphisms associated with the AML relapse and overall survival.
Ann Hematol. 2017; 96(1):93-98 [PubMed] Related Publications
The minichromosome maintenance complex component 7 (MCM7) encodes a member of MCM complex, which plays a critical role in the initiation of gene replication. Due to the importance of MCM complex, MCM7 gene has been regarded as a candidate gene for cancer development. In the present study, seven MCM7 polymorphisms were genotyped in 344 subjects composed of 103 acute myeloid leukemia (AML) patients and 241 normal controls to examine the possible associations between MCM7 polymorphisms and the risk of AML. MCM7 polymorphisms were not associated with the risk of AML (P > 0.05). However, MCM7 polymorphisms were significantly related to the relapse of AML and overall survival. The rs2070215 (N144S) showed a protective effect to the risk of AML relapse (OR = 0.37; P (corr) = 0.02). In haplotype analyses, the ht1 and ht2 showed significant associations with the risk of AML relapse (P (corr) = 0.02-0.03). In addition, rs1534309 showed an association with the overall survival of AML patients. Patients with major homozygote genotype (CC) of rs1534309 showed a higher survival rate than the patients with other genotypes (CG and GG). The results of the present study indicate that MCM7 polymorphisms may be able to predict the prognosis of AML patients.

Kim SH, Ho JN, Jin H, et al.
Upregulated expression of BCL2, MCM7, and CCNE1 indicate cisplatin-resistance in the set of two human bladder cancer cell lines: T24 cisplatin sensitive and T24R2 cisplatin resistant bladder cancer cell lines.
Investig Clin Urol. 2016; 57(1):63-72 [PubMed] Free Access to Full Article Related Publications
PURPOSE: The mechanism of resistance to cisplatin during treatment of bladder cancer (BC) has been a subject of intense investigation in clinical research. This study aims to identify candidate genes associated with resistance to cisplatin, in order to understand the resistance mechanism of BC cells to the drug, by combining the use of microarray profiling, quantitative reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analyses.
MATERIALS AND METHODS: The cisplatin sensitive human BC cell line (T24) and the cisplatin resistant BC cell line, T24R2, were used for microarray analysis to determine the differential expression of genes that are significant in cisplatin resistance. Candidate upregulated genes belonging to three well-known cancer-related KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways (p53 tumor suppressor, apoptosis, and cell cycle) were selected from the microarray data. These candidate genes, differentially expressed in T24 and T24R2, were then confirmed by quantitative RT-PCR and western blot. A fold change ≥2 with a p-value <0.05 was considered significant.
RESULTS: A total of 18 significantly upregulated genes were detected in the three selected cancer-related pathways in both microarray and RT-PCR analyses. These genes were PRKAR2A, PRKAR2B, CYCS, BCL2, BIRC3, DFFB, CASP6, CDK6, CCNE1, STEAP3, MCM7, ORC2, ORC5, ANAPC1, and ANAPC7, CDC7, CDC27, and SKP1. Western blot analyses also confirmed the upregulation of BCL2, MCM7, and CCNE1 at the protein level, indicating their crucial association with cisplatin resistance.
CONCLUSIONS: The BCL2, MCM7, and CCNE1 genes might play distinctive roles in cisplatin resistance in BC.

Jin Y, Dai Z
USO1 promotes tumor progression via activating Erk pathway in multiple myeloma cells.
Biomed Pharmacother. 2016; 78:264-71 [PubMed] Related Publications
OBJECTIVE: This study aimed to explore the influence of USO1 on multiple myeloma (MM) cell proliferation and apoptosis and the related molecular mechanism.
METHODS: The expression of USO1 and MIF in MM tissues and cells, normal bone marrow tissues and cells were determined by qRT-PCR and western blot assay. The cell proliferation and apoptosis of MM cells before and after knockdown of USO1 were determined by MTT assay and flow cytometry, respectively. Before and after knockdown of USO1, the expression of the proliferation-related genes cyclin D1, Mcm2 and PCNA in MM cells was determined by qRT-PCR and western blot assay. The protein level of p-Erk1/2 and MIF was determined by western blot assay and ELISA, respectively.
RESULTS: The expression levels of USO1 and MIF in MM tissues and cells were much higher than those in normal bone marrow tissues and cells. Knockdown of USO1 resulted in the inhibited ability of cell proliferation and induced cell apoptosis. The expression of cyclin D1, Mcm2, PCNA and p-Erk1/2 decreased significantly after knockdown of USO1 as well as the decreased MIF secretion.
CONCLUSION: USO1 gene may be a promising target for the therapy of human MM and its diagnosis marker.

Hiramatsu K, Yoshino K, Serada S, et al.
Similar protein expression profiles of ovarian and endometrial high-grade serous carcinomas.
Br J Cancer. 2016; 114(5):554-61 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Ovarian and endometrial high-grade serous carcinomas (HGSCs) have similar clinical and pathological characteristics; however, exhaustive protein expression profiling of these cancers has yet to be reported.
METHODS: We performed protein expression profiling on 14 cases of HGSCs (7 ovarian and 7 endometrial) and 18 endometrioid carcinomas (9 ovarian and 9 endometrial) using iTRAQ-based exhaustive and quantitative protein analysis.
RESULTS: We identified 828 tumour-expressed proteins and evaluated the statistical similarity of protein expression profiles between ovarian and endometrial HGSCs using unsupervised hierarchical cluster analysis (P<0.01). Using 45 statistically highly expressed proteins in HGSCs, protein ontology analysis detected two enriched terms and proteins composing each term: IMP2 and MCM2. Immunohistochemical analyses confirmed the higher expression of IMP2 and MCM2 in ovarian and endometrial HGSCs as well as in tubal and peritoneal HGSCs than in endometrioid carcinomas (P<0.01). The knockdown of either IMP2 or MCM2 by siRNA interference significantly decreased the proliferation rate of ovarian HGSC cell line (P<0.01).
CONCLUSIONS: We demonstrated the statistical similarity of the protein expression profiles of ovarian and endometrial HGSC beyond the organs. We suggest that increased IMP2 and MCM2 expression may underlie some of the rapid HGSC growth observed clinically.

Wang H, Qiu T, Shi J, et al.
Gene expression profiling analysis contributes to understanding the association between non-syndromic cleft lip and palate, and cancer.
Mol Med Rep. 2016; 13(3):2110-6 [PubMed] Free Access to Full Article Related Publications
The present study aimed to investigate the molecular mechanisms underlying non‑syndromic cleft lip, with or without cleft palate (NSCL/P), and the association between this disease and cancer. The GSE42589 data set was downloaded from the Gene Expression Omnibus database, and contained seven dental pulp stem cell samples from children with NSCL/P in the exfoliation period, and six controls. Differentially expressed genes (DEGs) were screened using the RankProd method, and their potential functions were revealed by pathway enrichment analysis and construction of a pathway interaction network. Subsequently, cancer genes were obtained from six cancer databases, and the cancer‑associated protein‑protein interaction network for the DEGs was visualized using Cytoscape. In total, 452 upregulated and 1,288 downregulated DEGs were screened. The upregulated DEGs were significantly enriched in the arachidonic acid metabolism pathway, including PTGDS, CYP4F2 and PLA2G16; and transforming growth factor (TGF)‑β signaling pathway, including SMAD3 and TGFB2. The downregulated DEGs were distinctly involved in the pathways of DNA replication, including MCM2 and POLA1; cell cycle, including CDK1 and STAG1; and viral carcinogenesis, including PIK3CA and HIST1H2BF. Furthermore, the pathways of cell cycle and viral carcinogenesis, with higher degrees of interaction were found to interact with other pathways, including DNA replication, transcriptional misregulation in cancer, and the TGF‑β signaling pathway. Additionally, TP53, CDK1, SMAD3, PIK3R1 and CASP3, with higher degrees, interacted with the cancer genes. In conclusion, the DEGs for NSCL/P were implicated predominantly in the TGF‑β signaling pathway, the cell cycle and in viral carcinogenesis. The TP53, CDK1, SMAD3, PIK3R1 and CASP3 genes were found to be associated, not only with NSCL/P, but also with cancer. These results may contribute to a better understanding of the molecular mechanisms of NSCL/P.

Wang B, Wang T, Cao XL, Li Y
Critical genes in head and neck squamous cell carcinoma revealed by bioinformatic analysis of gene expression data.
Genet Mol Res. 2015; 14(4):17406-15 [PubMed] Related Publications
In this study, bioinformatic analysis of gene expression data of head and neck squamous cell carcinoma (HNSCC) was performed to identify critical genes. Gene expression data of HNSCC were downloaded from the Cancer Genome Atlas (TCGA) and differentially expressed genes were determined through significance analysis of microarrays. Protein-protein interaction networks were constructed and used to identify hub genes. Functional enrichment analysis was performed with DAVID. Relevant microRNAs, transcription factors, and small molecule drugs were predicted by the Fisher exact test. Survival analysis was performed with the Kaplan-Meier plot from a package for survival analysis in R. In the five groups of HNSCC patients, a total of 5946 DEGs were identified in group 1, 4575 DEGs in group 2, 5580 DEGs in group 3, 8017 DEGs in group 4, and 5469 DEGs in group 5. DEGs in the cell cycle and immune response were significantly over-represented. Five PPI networks were constructed from which hub genes were acquired, such as minichromosome maintenance complex component 7 (MCM7), MCM2, decorin (DCN), retinoblastoma 1 (RB1), and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG). No significant difference in survival was observed among the 5 groups; however, a significant difference existed between two combined groups (groups 1, 3, and 5 vs groups 2 and 4). Our study revealed critical genes in HNSCC, which could supplement the knowledge about the pathogenesis of HNSCC and provide clues for future therapy development.

Borysov SI, Nepon-Sixt BS, Alexandrow MG
The N Terminus of the Retinoblastoma Protein Inhibits DNA Replication via a Bipartite Mechanism Disrupted in Partially Penetrant Retinoblastomas.
Mol Cell Biol. 2015; 36(5):832-45 [PubMed] Free Access to Full Article Related Publications
The N-terminal domain of the retinoblastoma (Rb) tumor suppressor protein (RbN) harbors in-frame exon deletions in partially penetrant hereditary retinoblastomas and is known to impair cell growth and tumorigenesis. However, how such RbN deletions contribute to Rb tumor- and growth-suppressive functions is unknown. Here we establish that RbN directly inhibits DNA replication initiation and elongation using a bipartite mechanism involving N-terminal exons lost in cancer. Specifically, Rb exon 7 is necessary and sufficient to target and inhibit the replicative CMG helicase, resulting in the accumulation of inactive CMGs on chromatin. An independent N-terminal loop domain, which forms a projection, specifically blocks DNA polymerase α (Pol-α) and Ctf4 recruitment without affecting DNA polymerases ε and δ or the CMG helicase. Individual disruption of exon 7 or the projection in RbN or Rb, as occurs in inherited cancers, partially impairs the ability of Rb/RbN to inhibit DNA replication and block G1-to-S cell cycle transit. However, their combined loss abolishes these functions of Rb. Thus, Rb growth-suppressive functions include its ability to block replicative complexes via bipartite, independent, and additive N-terminal domains. The partial loss of replication, CMG, or Pol-α control provides a potential molecular explanation for how N-terminal Rb loss-of-function deletions contribute to the etiology of partially penetrant retinoblastomas.

Yun J, Song SH, Kang JY, et al.
Reduced cohesin destabilizes high-level gene amplification by disrupting pre-replication complex bindings in human cancers with chromosomal instability.
Nucleic Acids Res. 2016; 44(2):558-72 [PubMed] Free Access to Full Article Related Publications
Gene amplification is a hallmark of cancer with chromosomal instability although the underlying mechanism by which altered copy numbers are maintained is largely unclear. Cohesin, involved in sister chromatid cohesion, DNA repair, cell cycle progression and transcriptional regulation of key developmental genes, is frequently overexpressed in human cancer. Here we show that cohesin-dependent change in DNA replication controls the copy numbers of amplified genes in cancer cells with chromosomal instability. We found that the down-regulation of elevated cohesin leads to copy number-associated gene expression changes without disturbing chromosomal segregation. Highly amplified genes form typical long-range chromatin interactions, which are stabilized by enriched cohesin. The spatial proximities among cohesin binding sites within amplified genes are decreased by RAD21-knockdown, resulting in the rapid decline of amplified gene expression. After several passages, cohesin depletion inhibits DNA replication initiation by reducing the recruitment of pre-replication complexes such as minichromosome maintenance subunits 7 (MCM7), DNA polymerase α, and CDC45 at replication origins near the amplified regions, and as a result, decreases the DNA copy numbers of highly amplified genes. Collectively, our data demonstrate that cohesin-mediated chromatin organization and DNA replication are important for stabilizing gene amplification in cancer cells with chromosomal instability.

Qu GQ, Lu YM, Liu YF, et al.
Effect of RTKN on progression and metastasis of colon cancer in vitro.
Biomed Pharmacother. 2015; 74:117-23 [PubMed] Related Publications
Like many epithelial-derived cancers, colon cancer results from a multistep tumorigenic process. However, the detailed mechanisms involved in colon cancer formations are poorly characterized. In the present study, we investigated the role of RTKN in colon cancer and explored underlying mechanisms. The results showed that RTKN expression was significantly increased in colon cancer tissues when compared with the adjacent tissues of patients in Shanghai People's hospital and in TCGA independent dataset. Furthermore, silencing of RTKN inhibited cell proliferation, migration, invasion, and arrested cell cycle at G1 phase in LOVO cells. Bioinformatics analysis demonstrated that DNA replication and cell cycle were involved in the regulation of RTKN. MCM2/3/5, CDK1/2 and PCNA expression had a direct relationship with the reduction of RTKN. RTKN could affect the proliferation and metastasis of colon cancer by reducing expression of MCM2/3/5, CDK1/2 and PCNA, suggesting that RTKN was a potential target for treating colon cancer.

Zhang Y, Zhang J, Liu Z, et al.
A network-based approach to identify disease-associated gene modules through integrating DNA methylation and gene expression.
Biochem Biophys Res Commun. 2015; 465(3):437-42 [PubMed] Related Publications
Formation and progression of complex diseases are generally the joint effect of genetic and epigenetic disorders, thus an integrative analysis of epigenetic and genetic data is essential for understanding mechanism of the diseases. In this study, we integrate Illuminate 450k DNA methylation and gene expression data to calculate the weights of gene network using Principal Component Analysis (PCA) and Canonical Correlation Analysis (CCA). The approach considers all methylation values of CpG sites in a gene, rather than averaging them which was used in other studies ignoring the variability of the methylation sites. Through comparing topological features of control network with those of case network, including global and local features, candidate disease-associated genes and gene modules are identified. We apply the approach to real data, breast invasive carcinoma (BRCA). It successfully identifies susceptibility breast cancer-related genes, such as TP53, BRCA1, EP300, CDK2, MCM7 and so forth, within which most are previously known to breast cancer. Also, GO and pathway enrichment analysis indicate that these genes enrich in cell apoptosis and regulation of cell death which are cancer-related biological processes. Importantly, through analyzing the functions and comparing expression and methylation values of these genes between cases and controls, we find some genes, such as VASN, SNRPD3, and gene modules, targeted by POLR2C, CHMP1B and TAF9, which might be novel breast cancer-related biomarkers.

Wage J, Ma L, Peluso M, et al.
Proton irradiation impacts age-driven modulations of cancer progression influenced by immune system transcriptome modifications from splenic tissue.
J Radiat Res. 2015; 56(5):792-803 [PubMed] Free Access to Full Article Related Publications
Age plays a crucial role in the interplay between tumor and host, with additional impact due to irradiation. Proton irradiation of tumors induces biological modulations including inhibition of angiogenic and immune factors critical to 'hallmark' processes impacting tumor development. Proton irradiation has also provided promising results for proton therapy in cancer due to targeting advantages. Additionally, protons may contribute to the carcinogenesis risk from space travel (due to the high proportion of high-energy protons in space radiation). Through a systems biology approach, we investigated how host tissue (i.e. splenic tissue) of tumor-bearing mice was altered with age, with or without whole-body proton exposure. Transcriptome analysis was performed on splenic tissue from adolescent (68-day) versus old (736-day) C57BL/6 male mice injected with Lewis lung carcinoma cells with or without three fractionations of 0.5 Gy (1-GeV) proton irradiation. Global transcriptome analysis indicated that proton irradiation of adolescent hosts caused significant signaling changes within splenic tissues that support carcinogenesis within the mice, as compared with older subjects. Increases in cell cycling and immunosuppression in irradiated adolescent hosts with CDK2, MCM7, CD74 and RUVBL2 indicated these were the key genes involved in the regulatory changes in the host environment response (i.e. the spleen). Collectively, these results suggest that a significant biological component of proton irradiation is modulated by host age through promotion of carcinogenesis in adolescence and resistance to immunosuppression, carcinogenesis and genetic perturbation associated with advancing age.

An F, Zhang Z, Xia M, Xing L
Subpath analysis of each subtype of head and neck cancer based on the regulatory relationship between miRNAs and biological pathways.
Oncol Rep. 2015; 34(4):1745-54 [PubMed] Related Publications
The aim of the present study was to explore the potential mechanisms involved in each subtype of head and neck squamous cell carcinoma (HNSCC) via subpath analysis and to investigate their relevance in the prevention of HNSCC. Gene expression profiles of GSE6631 and GSE39366 containing 44 and 168 HNSCC samples, respectively, were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) from samples in GSE6631 and GSE393666 were screened using the Detection of Imbalanced Differential Signal (DIDS) method respectively. DEGs in GSE39366 were matched with the DEGs in GSE6631 and were used to classify the subtypes of HNSCC based on hierarchical clustering analysis. Furthermore, DEGs were separated into different subtypes and then the pathway information was analyzed. The regulated miRNAs for the DEGs in each subtype were analyzed to select the significant subpaths. Totally, 1,095 DEGs from GSE6631 and 2,528 DEGs from GSE39366 were screened. Samples in GSE39366 were separated into four subtypes. Specific genes in each subtype and DEGs in the common gene set involved in a variety of pathways were identified. In addition, the significant miRNA-target-pathway subpath of each subtype of HNSCC and the common gene set of HNSCC were also enriched. Our data suggest that human papillomavirus (HPV) is positively correlated with HNSCC in subtype 2. Several miRNAs (miRLet-7A, miR-1, miR-206, miR-153, miR-519A and miR-506) and their target genes (CYP46A1, BPNT1, MCM7 and COL5A1) are crucial for HNSCC prevention via different pathways and may provide further knowledge of the mechanisms involved in the progression of HNSCC.

Nishikawa R, Goto Y, Kurozumi A, et al.
MicroRNA-205 inhibits cancer cell migration and invasion via modulation of centromere protein F regulating pathways in prostate cancer.
Int J Urol. 2015; 22(9):867-77 [PubMed] Related Publications
OBJECTIVES: To investigate the functional roles of microRNA-205 in the modulation of novel cancer pathways in prostate cancer cells.
METHODS: Functional studies of microRNA-205 were carried out to investigate cell proliferation, migration and invasion in prostate cancer cell lines (PC3 and DU145) by restoration of mature microRNA. In silico database and genome-wide gene expression analyses were carried out to identify molecular targets and pathways mediated by microRNA-205. Loss-of-function studies were applied to microRNA-205 target genes.
RESULTS: Restoration of microRNA-205 in cancer cell lines significantly inhibited cancer cell migration and invasion. Our data showed that the centromere protein F gene was overexpressed in prostate cancer clinical specimens and was a direct target of microRNA-205 regulation. Silencing of centromere protein F significantly inhibited cancer cell migration and invasion. Furthermore, MCM7, an oncogenic gene functioning downstream of centromere protein F, was identified by si-centromere protein F transfectants in prostate cancer cells.
CONCLUSIONS: Loss of tumor-suppressive microRNA-205 seems to enhance cancer cell migration and invasion in prostate cancer through direct regulation of centromere protein F. Our data describing pathways regulated by tumor-suppressive microRNA-205 provide new insights into the potential mechanisms of prostate cancer oncogenesis and metastasis.

Jian T, Chen Y
Regulatory mechanisms of transcription factors and target genes on gastric cancer by bioinformatics method.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):524-8 [PubMed] Related Publications
BACKGROUND/AIMS: Gastric cancer is one of the most lethal diseases and has caused a global health problem. We aimed to elucidate the major mechanisms involved in the gastric cancer progression.
METHODOLOGY: The expression profile GSE13911 was downloaded from GEO database, composing of 31 normal and 38 tumor samples. The transcription factor (TF)--target gene regulatory network and protein-protein interaction (PPI) network related to gastric cancer were obtained from TRED and TRANSFAC databases. After combining the two networks, we constructed an integrated network.
RESULTS: In total, 5255 DEGs in tumor samples were identified, which were mainly enriched in 12 pathways including cell cycle. The integrated network of TF--target gene--protein interaction included 7 genes related to cell cycle, in which E2F1 was predicted to mediate the expression of MCM4, MCM5 and CDC6 through regulating the expression of its target gene MCM3.
CONCLUSION: In gastric cancer progression, E2F1 may play vital roles in the involvement of cell cycle pathway through regulating its target gene MCM3, which might interact with MCM4, MCM5 and MCM7. Besides, STAT1 was another potentially critical transcription factor which could regulate multiple target genes.

Kunnev D, Freeland A, Qin M, et al.
Effect of minichromosome maintenance protein 2 deficiency on the locations of DNA replication origins.
Genome Res. 2015; 25(4):558-69 [PubMed] Free Access to Full Article Related Publications
Minichromosome maintenance (MCM) proteins are loaded onto chromatin during G1-phase and define potential locations of DNA replication initiation. MCM protein deficiency results in genome instability and high rates of cancer in mouse models. Here we develop a method of nascent strand capture and release and show that MCM2 deficiency reduces DNA replication initiation in gene-rich regions of the genome. DNA structural properties are shown to correlate with sequence motifs associated with replication origins and with locations that are preferentially affected by MCM2 deficiency. Reduced nascent strand density correlates with sites of recurrent focal CNVs in tumors arising in MCM2-deficient mice, consistent with a direct relationship between sites of reduced DNA replication initiation and genetic damage. Between 10% and 90% of human tumors, depending on type, carry heterozygous loss or mutation of one or more MCM2-7 genes, which is expected to compromise DNA replication origin licensing and result in elevated rates of genome damage at a subset of gene-rich locations.

Zheng J
Diagnostic value of MCM2 immunocytochemical staining in cervical lesions and its relationship with HPV infection.
Int J Clin Exp Pathol. 2015; 8(1):875-80 [PubMed] Free Access to Full Article Related Publications
Cervical cancer remains the fourth most common cause of cancer-related deaths in women worldwide, and human papillomavirus infection represents the most important risk factor for the development of cervical cancer. Minichromosome maintenance protein-2 has been previously identified by DNA microarray and transcriptional profiling as genes that is overexpressed in cervical carcinomas. 183 cases were enrolled and tested with thin prep liquid-based cytology test. The expressions of human papillomavirus were detected and minichromosome maintenance protein-2 immuncytochemical test was performed on liquid-based pap smears from the samples. Those results were compared with the cervical histopathology results. The positive expression rates of minichromosome maintenance protein-2 and high-risk type human papillomavirus increased with the severity of cervical lesions. The expression level of MCM2 was positively correlated with high-risk types of human papillomavirus. In cervical carcinoma and precancerous lesions, minichromosome maintenance protein-2 was overexpressed and positively correlated with the high risk types of human papillomavirus. As minichromosome maintenance protein-2 immuncytochemical detection was better than genotyping of human papillomavirus, minichromosome maintenance protein-2 may serve as a useful marker in the screening of cervical carcinoma and precancerous lesions and improve the diagnosis of atypical squamous cell of undetermined significance. The joint application can improve the sensitivity and specificity of diagnosis.

Floriano PN, Abram T, Taylor L, et al.
Programmable bio-nanochip-based cytologic testing of oral potentially malignant disorders in Fanconi anemia.
Oral Dis. 2015; 21(5):593-601 [PubMed] Free Access to Full Article Related Publications
Fanconi anemia (FA) is caused by mutations of DNA repair genes. The risk of oral squamous cell carcinoma (OSCC) among FA patients is 800-folds higher than in the general population. Early detection of OSCC, preferably at it precursor stage, is critical in FA patients to improve their survival. In an ongoing clinical trial, we are evaluating the effectiveness of the programmable bio-nanochip (p-BNC)-based oral cytology test in diagnosing oral potentially malignant disorders (OPMD) in non-FA patients. We used this test to compare cytomorphometric and molecular biomarkers in OSCC cell lines derived from FA and non-FA patients to brush biopsy samples of a FA patient with OPMD and normal mucosa of healthy volunteers. Our data showed that expression patterns of molecular biomarkers were not notably different between sporadic and FA-OSCC cell lines. The p-BNC assay revealed significant differences in cytometric parameters and biomarker MCM2 expression between cytobrush samples of the FA patient and cytobrush samples of normal oral mucosa obtained from healthy volunteers. Microscopic examination of the FA patient's OPMD confirmed the presence of dysplasia. Our pilot data suggests that the p-BNC brush biopsy test recognized dysplastic oral epithelial cells in a brush biopsy sample of a FA patient.

Ishimi Y, Irie D
G364R mutation of MCM4 detected in human skin cancer cells affects DNA helicase activity of MCM4/6/7 complex.
J Biochem. 2015; 157(6):561-9 [PubMed] Related Publications
A number of gene mutations are detected in cells derived from human cancer tissues, but roles of these mutations in cancer cell development are largely unknown. We examined G364R mutation of MCM4 detected in human skin cancer cells. Formation of MCM4/6/7 complex is not affected by the mutation. Consistent with this notion, the binding to MCM6 is comparable between the mutant MCM4 and wild-type MCM4. Nuclear localization of this mutant MCM4 expressed in HeLa cells supports this conclusion. Purified MCM4/6/7 complex containing the G364R MCM4 exhibited similar levels of single-stranded DNA binding and ATPase activities to the complex containing wild-type MCM4. However, the mutant complex showed only 30-50% of DNA helicase activity of the wild-type complex. When G364R MCM4 was expressed in HeLa cells, it was fractionated into nuclease-sensitive chromatin fraction, similar to wild-type MCM4. These results suggest that this mutation does not affect assembly of MCM2-7 complex on replication origins but it interferes some step at function of MCM2-7 helicase. Thus, this mutation may contribute to cancer cell development by disturbing DNA replication.

Liang JW, Shi ZZ, Shen TY, et al.
Identification of genomic alterations in pancreatic cancer using array-based comparative genomic hybridization.
PLoS One. 2014; 9(12):e114616 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Genomic aberration is a common feature of human cancers and also is one of the basic mechanisms that lead to overexpression of oncogenes and underexpression of tumor suppressor genes. Our study aims to identify frequent genomic changes in pancreatic cancer.
MATERIALS AND METHODS: We used array comparative genomic hybridization (array CGH) to identify recurrent genomic alterations and validated the protein expression of selected genes by immunohistochemistry.
RESULTS: Sixteen gains and thirty-two losses occurred in more than 30% and 60% of the tumors, respectively. High-level amplifications at 7q21.3-q22.1 and 19q13.2 and homozygous deletions at 1p33-p32.3, 1p22.1, 1q22, 3q27.2, 6p22.3, 6p21.31, 12q13.2, 17p13.2, 17q21.31 and 22q13.1 were identified. Especially, amplification of AKT2 was detected in two carcinomas and homozygous deletion of CDKN2C in other two cases. In 15 independent validation samples, we found that AKT2 (19q13.2) and MCM7 (7q22.1) were amplified in 6 and 9 cases, and CAMTA2 (17p13.2) and PFN1 (17p13.2) were homozygously deleted in 3 and 1 cases. AKT2 and MCM7 were overexpressed, and CAMTA2 and PFN1 were underexpressed in pancreatic cancer tissues than in morphologically normal operative margin tissues. Both GISTIC and Genomic Workbench software identified 22q13.1 containing APOBEC3A and APOBEC3B as the only homozygous deletion region. And the expression levels of APOBEC3A and APOBEC3B were significantly lower in tumor tissues than in morphologically normal operative margin tissues. Further validation showed that overexpression of PSCA was significantly associated with lymph node metastasis, and overexpression of HMGA2 was significantly associated with invasive depth of pancreatic cancer.
CONCLUSION: These recurrent genomic changes may be useful for revealing the mechanism of pancreatic carcinogenesis and providing candidate biomarkers.

Montes de Oca R, Gurard-Levin ZA, Berger F, et al.
The histone chaperone HJURP is a new independent prognostic marker for luminal A breast carcinoma.
Mol Oncol. 2015; 9(3):657-74 [PubMed] Related Publications
BACKGROUND: Breast cancer is a heterogeneous disease with different molecular subtypes that have varying responses to therapy. An ongoing challenge in breast cancer research is to distinguish high-risk patients from good prognosis patients. This is particularly difficult in the low-grade, ER-positive luminal A tumors, where robust diagnostic tools to aid clinical treatment decisions are lacking. Recent data implicating chromatin regulators in cancer initiation and progression offers a promising avenue to develop new tools to help guide clinical decisions.
METHODS: Here we exploit a published transcriptome dataset and an independent validation cohort to correlate the mRNA expression of selected chromatin regulators with respect to the four intrinsic breast cancer molecular subtypes. We then perform univariate and multivariate analyses to compare the prognostic value of a panel of chromatin regulators to Ki67, a currently utilized proliferation marker.
RESULTS: Unsupervised hierarchical clustering revealed a gene cluster containing several histone chaperones and histone variants highly-expressed in the proliferative subtypes (basal-like, HER2-positive, luminal B) but not in the luminal A subtype. Several chromatin regulators, including the histone chaperones CAF-1 (subunits p150 and p60), ASF1b, and HJURP, and the centromeric histone variant CENP-A, associated with local and metastatic relapse and poor patient outcome. Importantly, we find that HJURP can discriminate favorable and unfavorable outcome within the luminal A subtype, outperforming the currently utilized proliferation marker Ki67, as an independent prognostic marker for luminal A patients.
CONCLUSIONS: The integration of chromatin regulators as clinical biomarkers, in particular the histone chaperone HJURP, will help guide patient substratification and treatment options for low-risk luminal A breast carcinoma patients.

Yang H, Lan P, Hou Z, et al.
Histone deacetylase inhibitor SAHA epigenetically regulates miR-17-92 cluster and MCM7 to upregulate MICA expression in hepatoma.
Br J Cancer. 2015; 112(1):112-21 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Epigenetic therapy using histone deacetylase inhibitors (HDACi) has shown promise in clinical trials for the treatment of human malignancies. In addition to the immediate effects on the tumour cell growth, HDACi upregulates the expression of MHC class I-related chain molecules A and B (MICA and MICB), resulting in an enhanced susceptibility of tumour cells to natural killer cell-mediated lysis. The molecular mechanism underlying is still unclear.
METHODS: The transcriptional regulation mechanism underlying suberoylanilide hydroxamic acid (SAHA)-mediated regulation of MICA and related miRNA expression was investigated using promoter acetylation assays, bioinformatics analysis and chromatin immunoprecipitation assay.
RESULTS: SAHA upregulates the transcription of MICA/B by promoting MICA-associated histone acetylation while suppressing the MICA/B-targeting miRNAs miR-20a, miR-93 and miR-106b. The mechanism by which SAHA repressed miRNAs transcription involved repression of their host genes (miR-17-92 cluster and MCM7). SAHA downregulated the miR-17-92 cluster by abolishing tyrosine phosphorylation of STAT3 and decreased MCM7 transcription through localised histone deacetylation.
CONCLUSIONS: The HDACi SAHA epigenetically upregulates MICA expression through regulating the expression of miR-17-92 cluster and MCM7 in hepatoma, thus enhancing the sensitivity of HCC to natural killer cell-mediated lysis. This novel mechanism of action provides promise for HDACi in therapy of HCC.

Zhang L, Yang B, Zhou K, et al.
Potential therapeutic mechanism of genistein in breast cancer involves inhibition of cell cycle regulation.
Mol Med Rep. 2015; 11(3):1820-6 [PubMed] Free Access to Full Article Related Publications
Genistein can prevent tumorigenesis and reduce the incidence of diseases that are dependent upon estrogen. Previous research, however, has shown that genistein can also increase the risk of breast cancer. Thus, the aim of the present study was to investigate the mechanism underlying the effect of genistein in breast cancer and to determine whether genistein produces a therapeutic effect or promotes the development of breast cancer. Gene microarray data obtained from three samples treated with alcohol (control group), three samples treated with 3 µmol/l genistein and three samples treated with 10 µmol/l genistein for 48 h, were downloaded from the Gene Expression Omnibus database. Analysis of the differentially expressed genes (DEGs) and functional enrichment in the two genistein groups was performed. The interaction networks of the DEGs were constructed and the overlapping network was extracted. Finally, the functions and pathways of the DEGs in the overlapping network were enriched. In total, 224 DEGs coexisted in the two genistein groups, and the most significant function of these was the cell cycle. The number and the fold change of expression values of the DEGs in the 10 µmol/l genistein group were significantly higher compared with that of the 3 µmol/l genistein group. The most significant function and pathway of the DEGs in the overlapping network was the cell cycle involving several genes, including GLIPR1, CDC20, BUB1, MCM2 and CCNB1. Thus, genistein stimulation resulted in gene expression changes in breast cancer cell lines and discrepancies increased with higher doses of genistein. The DEGs were most significantly associated with cell cycle regulation.

McCann MJ, Rowland IR, Roy NC
The anti-proliferative effects of enterolactone in prostate cancer cells: evidence for the role of DNA licencing genes, mi-R106b cluster expression, and PTEN dosage.
Nutrients. 2014; 6(11):4839-55 [PubMed] Free Access to Full Article Related Publications
The mammalian lignan, enterolactone, has been shown to reduce the proliferation of the earlier stages of prostate cancer at physiological concentrations in vitro. However, efficacy in the later stages of the disease occurs at concentrations difficult to achieve through dietary modification. We have therefore investigated what concentration(s) of enterolactone can restrict proliferation in multiple stages of prostate cancer using an in vitro model system of prostate disease. We determined that enterolactone at 20 μM significantly restricted the proliferation of mid and late stage models of prostate disease. These effects were strongly associated with changes in the expression of the DNA licencing genes (GMNN, CDT1, MCM2 and 7), in reduced expression of the miR-106b cluster (miR-106b, miR-93, and miR-25), and in increased expression of the PTEN tumour suppressor gene. We have shown anti-proliferative effects of enterolactone in earlier stages of prostate disease than previously reported and that these effects are mediated, in part, by microRNA-mediated regulation.

Young A, Berry R, Holloway AF, et al.
RNA-seq profiling of a radiation resistant and radiation sensitive prostate cancer cell line highlights opposing regulation of DNA repair and targets for radiosensitization.
BMC Cancer. 2014; 14:808 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Radiotherapy is a chosen treatment option for prostate cancer patients and while some tumours respond well, up to 50% of patients may experience tumour recurrence. Identification of functionally relevant predictive biomarkers for radioresponse in prostate cancer would enable radioresistant patients to be directed to more appropriate treatment options, avoiding the side-effects of radiotherapy.
METHODS: Using an in vitro model to screen for novel biomarkers of radioresistance, transcriptome analysis of a radioresistant (PC-3) and radiosensitive (LNCaP) prostate cancer cell line was performed. Following pathway analysis candidate genes were validated using qRT-PCR. The DNA repair pathway in radioresistant PC-3 cells was then targeted for radiation sensitization using the PARP inhibitor, niacinimide.
RESULTS: Opposing regulation of a DNA repair and replication pathway was observed between PC-3 and LNCaP cells from RNA-seq analysis. Candidate genes BRCA1, RAD51, FANCG, MCM7, CDC6 and ORC1 were identified as being significantly differentially regulated post-irradiation. qRT-PCR validation confirmed BRCA1, RAD51 and FANCG as being significantly differentially regulated at 24 hours post radiotherapy (p-value =0.003, 0.045 and 0.003 respectively). While the radiosensitive LNCaP cells down-regulated BRCA1, FANCG and RAD51, the radioresistant PC-3 cell line up-regulated these candidates to promote cell survival post-radiotherapy and a similar trend was observed for MCM7, CDC6 and ORC1. Inhibition of DNA repair using niacinamide sensitised the radioresistant cells to irradiation, reducing cell survival at 2 Gy from 66% to 44.3% (p-value =0.02).
CONCLUSIONS: These findings suggest that the DNA repair candidates identified via RNA-seq hold potential as both targets for radiation sensitization and predictive biomarkers in prostate cancer.

Xiao X, Zhou L, Cao P, et al.
MicroRNA-93 regulates cyclin G2 expression and plays an oncogenic role in laryngeal squamous cell carcinoma.
Int J Oncol. 2015; 46(1):161-74 [PubMed] Related Publications
microRNA93 (miR-93) is expressed in the miR‑106b-25 cluster, located in intron 13 of the MCM7 gene. Our previous study found that miR-93 was significantly upregulated in laryngeal squamous cell carcinoma (LSCC), and cyclin G2 (CCNG2) was a potential target of miR-93 in LSCC. However, the possible functions and molecular mechanisms of miR-93 in LSCC remain unknown. In the present study, we show that the level of CCNG2 protein expression was significantly lower in LSCC cancer tissue than normal tissues. The level of CCNG2 was correlated with clinical stages, lymph node metastasis and histological grade. We further show that the expression level of miR-93 was inversely correlated with CCNG2 expression in clinical specimens. Furthermore, gain-of-function assays revealed that miR-93 promoted cell proliferation, decreased apoptosis rates, induced cell cycle arrest and promoted cell migration and invasion, whereas silencing of miR-93 attenuated these carcinogenic processes. In addition, overexpression of miR-93 in Hep-2 cells could reduce the mRNA and protein levels of CCNG2, whereas silencing of miR-93 in Hep-2 cells significantly increased CCNG2 expression. A luciferase assay verified that miR-93 could bind to the 3' untranslated region of CCNG2. Importantly, ectopic expression of CCNG2 in miR-93 cells rescued the effect of miR-93 on LSCC proliferation. Knockdown of CCNG2 promoted cell proliferation resembling that of miR-93 overexpression. These findings demonstrated that miR-93 promotes tumor growth by directly suppressing CCNG2. Taken together, these results suggested that this newly identified miR-93-CCNG2 axis may be involved in LSCC proliferation and progression. Our findings provide novel potential targets for LSCC therapy and prognosis.

Wu HL, Heneidi S, Chuang TY, et al.
The expression of the miR-25/93/106b family of micro-RNAs in the adipose tissue of women with polycystic ovary syndrome.
J Clin Endocrinol Metab. 2014; 99(12):E2754-61 [PubMed] Free Access to Full Article Related Publications
CONTEXT: In adipose tissue (AT) micro-RNA-93 (miR-93) is significantly overexpressed in polycystic ovary syndrome (PCOS) women and non-PCOS women with insulin resistance (IR). Overexpressed miR-93 directly inhibits glucose transporter isoform 4, impairing both glucose metabolism and insulin sensitivity. The mechanisms behind increased miR-93 expression are unclear.
OBJECTIVE: Our objective was to determine whether miR-93 expression is concordant with its host gene, MCM7, which contains the miR-25/93/106b gene cluster.
PATIENTS: AT was excised from 16 women with PCOS (eight with and eight without IR) and 15 non-PCOS (nine with and six without IR).
MAIN OUTCOME MEASURES: Expression of MCM7 and miR-25/93/106b was measured in AT and 3T3-L1 cells.
RESULTS: MCM7 expression was lower in both non-PCOS/IR and PCOS women and tended to be lowest in women with PCOS and IR. Overall, the expression of MCM7 in human AT was negatively associated with miR-93 expression and with increased subject IR. Additionally, miR-25 and miR-106b expression is uncoupled from the MCM7 host gene and are positively correlated with IR, although no PCOS-specific difference was observed. MCM7 expression appears to be negatively correlated with increasing fasting glucose. In 3T3-L1 adipocytes, increasing glucose had no effect on miR-93 or miR-25, although it reduced MCM7 and increased miR-106b expression in a dose-dependent fashion. In turn, in 3T3-L1 adipocytes, increasing insulin had no effect on either MCM7 or miR-25/93/106b expression.
CONCLUSIONS: Our data suggest that the expression of MCM7 and miR-93/25 is PCOS and IR related, whereas that of miR-106b is related to IR only. In 3T3-L1 adipocytes, neither hyperglycemia nor hyperinsulinemia altered the expression of miR-93 or miR-25, although increasing glucose levels down-regulated MCM7 and paradoxically increased that of miR-106b expression. The expression of the miR-25/93/106b family may be regulated through mechanisms distinct from its host gene, MCM7. Finally, our studies suggest potential epigenetic mechanisms for both IR and PCOS.

Hoskins JW, Jia J, Flandez M, et al.
Transcriptome analysis of pancreatic cancer reveals a tumor suppressor function for HNF1A.
Carcinogenesis. 2014; 35(12):2670-8 [PubMed] Free Access to Full Article Related Publications
Pancreatic ductal adenocarcinoma (PDAC) is driven by the accumulation of somatic mutations, epigenetic modifications and changes in the micro-environment. New approaches to investigating disruptions of gene expression networks promise to uncover key regulators and pathways in carcinogenesis. We performed messenger RNA-sequencing in pancreatic normal (n = 10) and tumor (n = 8) derived tissue samples, as well as in pancreatic cancer cell lines (n = 9), to determine differential gene expression (DE) patterns. Sub-network enrichment analyses identified HNF1A as the regulator of the most significantly and consistently dysregulated expression sub-network in pancreatic tumor tissues and cells (median P = 7.56×10(-7), median rank = 1, range = 1-25). To explore the effects of HNF1A expression in pancreatic tumor-derived cells, we generated stable HNF1A-inducible clones in two pancreatic cancer cell lines (PANC-1 and MIA PaCa-2) and observed growth inhibition (5.3-fold, P = 4.5×10(-5) for MIA PaCa-2 clones; 7.2-fold, P = 2.2×10(-5) for PANC-1 clones), and a G0/G1 cell cycle arrest and apoptosis upon induction. These effects correlated with HNF1A-induced down-regulation of 51 of 84 cell cycle genes (e.g. E2F1, CDK2, CDK4, MCM2/3/4/5, SKP2 and CCND1), decreased expression of anti-apoptotic genes (e.g. BIRC2/5/6 and AKT) and increased expression of pro-apoptotic genes (e.g. CASP4/9/10 and APAF1). In light of the established role of HNF1A in the regulation of pancreatic development and homeostasis, our data suggest that it also functions as an important tumor suppressor in the pancreas.

Kashkin K, Chernov I, Stukacheva E, et al.
Cancer specificity of promoters of the genes controlling cell proliferation.
J Cell Biochem. 2015; 116(2):299-309 [PubMed] Related Publications
Violation of proliferation control is a common feature of cancer cells. We put forward the hypothesis that promoters of genes involved in the control of cell proliferation should possess intrinsic cancer specific activity. We cloned promoter regions of CDC6, POLD1, CKS1B, MCM2, and PLK1 genes into pGL3 reporter vector and studied their ability to drive heterologous gene expression in transfected cancer cells of different origin and in normal human fibroblasts. Each promoter was cloned in short (335-800 bp) and long (up to 2.3 kb) variants to cover probable location of core and whole promoter regulatory elements. Cloned promoters were significantly more active in cancer cells than in normal fibroblasts that may indicate their cancer specificity. Both versions of CDC6 promoters were shown to be most active while the activities of others were close to that of BIRC5 gene (survivin) gene promoter. Long and short variants of each cloned promoter demonstrated very similar cancer specificity with the exception of PLK1-long promoter that was substantially more specific than its short variant and other promoters under study. The data indicate that most of the important cis-regulatory transcription elements responsible for intrinsic cancer specificity are located in short variants of the promoters under study. CDC6 short promoter may serve as a promising candidate for transcription targeted cancer gene therapy.

Cheung CC, Chung GT, Lun SW, et al.
miR-31 is consistently inactivated in EBV-associated nasopharyngeal carcinoma and contributes to its tumorigenesis.
Mol Cancer. 2014; 13:184 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: As a distinctive type of head and neck cancers, nasopharyngeal carcinoma (NPC) is genesis from the clonal Epstein-Barr virus (EBV)-infected nasopharyngeal epithelial cells accumulated with multiple genetic lesions. Among the recurrent genetic alterations defined, loss of 9p21.3 is the most frequent early event in the tumorigenesis of EBV-associated NPC. In addition to the reported CDKN2A/p16, herein, we elucidated the role of a miRNA, miR-31 within this 9p21.3 region as NPC-associated tumor suppressor.
METHODS: The expression and promoter methylation of miR-31 were assessed in a panel of NPC tumor lines and primary tumors. Its in vitro and in vivo tumor suppression function was investigated through the ectopic expression of miR-31 in NPC cells. We also determined the miR-31 targeted genes and its involvement in the growth in NPC.
RESULTS: Downregulation of miR-31 expression was detected in almost all NPC cell line, patient-derived xenografts (PDXs) and primary tumors. Both homozygous deletion and promoter hypermethylation were shown to be major mechanisms for miR-31 silencing in this cancer. Strikingly, loss of miR-31 was also obviously observed in the dysplastic lesions of nasopharynx. Restoration of miR-31 in C666-1 cells inhibited the cell proliferation, colony-forming and migratory capacities. Dramatic reduction of in vitro anchorage-independent growth and in vivo tumorigenic potential were demonstrated in the stable clones expressing miR-31. Furthermore, we proved that miR-31 suppressed the NPC cell growth via targeting FIH1 and MCM2.
CONCLUSIONS: The findings provide strong evidence to support miR-31 as a new NPC-associated tumor suppressor on 9p21.3 region. The inactivation of miR-31 may contribute to the early development of NPC.

Zhang W, Gong W, Ai H, et al.
Gene expression analysis of lung adenocarcinoma and matched adjacent non-tumor lung tissue.
Tumori. 2014 May-Jun; 100(3):338-45 [PubMed] Related Publications
AIMS AND BACKGROUND: The aim of this study was to find disease-associated genes and gene functions in lung adenocarcinoma and matched adjacent non-tumor lung tissues with DNA microarray.
METHODS: We downloaded the gene expression profile GSE32863 from the Gene Expression Omnibus database including 58 lung adenocarcinoma and 58 adjacent non-tumor lung tissue samples. Data were preprocessed and the differentially expressed genes (DEGs) were identified using packages in the R computing language. The selected DEGs were further analyzed with bioinformatics methods. After the coexpression network of DEGs was constructed by STRING (Search Tool for the Retrieval of Interacting Genes/Proteins), we analyzed gene functions with DAVID (The Database for Annotation, Visualization and Integrated Discovery) and WebGestalt (WEB-based Gene Set Analysis Toolkit).
RESULTS: A total of 1429 genes were filtered as DEGs, including 873 downregulated genes and 556 upregulated genes, and the DEGs including CDC45, CCNB2, CDC20, MCM2, PTTG1, MCM4 and FEN1 were most significantly related to cell cycle and DNA replication.
CONCLUSION: The discovery of featured genes which were significantly related to cell cycle and DNA replication has potential for use in the clinic for the diagnosis of lung adenocarcinoma in the future. However, further experiments will be needed to confirm our result.

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