Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic. Tag cloud generated 07 March, 2017 using data from PubMed, MeSH and CancerIndex
Mutated Genes and Abnormal Protein Expression (39)
Clicking on the Gene or Topic will take you to a separate more detailed page. Sort this list by clicking on a column heading e.g. 'Gene' or 'Topic'.
|NODAL ||10q22.1 ||HTX5 || ||-NODAL and Oral Cavity Cancer || 87|
|GSTM1 ||1p13.3 ||MU, H-B, GST1, GTH4, GTM1, MU-1, GSTM1-1, GSTM1a-1a, GSTM1b-1b || ||-GSTM1 and Oral Cavity Cancer || 72|
|BAX ||19q13.33 ||BCL2L4 || ||-BAX and Oral Cavity Cancer || 44|
|MMP2 ||16q12.2 ||CLG4, MONA, CLG4A, MMP-2, TBE-1, MMP-II || ||-MMP2 and Oral Cancer || 44|
|GSTT1 ||22q11.23 || || ||-GSTT1 and Oral Cavity Cancer || 40|
|CA9 ||9p13.3 ||MN, CAIX || ||-CA9 and Oral Cavity Cancer || 34|
|BCL2 ||18q21.3 ||Bcl-2, PPP1R50 || ||-BCL2 and Oral Cavity Cancer || 13|
|NAT2 ||8p22 ||AAC2, PNAT, NAT-2 || ||-NAT2 and Oral Cancer || 13|
|FGF4 ||11q13.3 ||HST, KFGF, HST-1, HSTF1, K-FGF, HBGF-4 || ||-FGF4 and Oral Cavity Cancer || 11|
|GSTM3 ||1p13.3 ||GST5, GSTB, GTM3, GSTM3-3 || ||-GSTM3 and Oral Cavity Cancer || 11|
|MARCO ||2q14.2 ||SCARA2 || ||-MARCO and Oral Cavity Cancer || 11|
|CTTN ||11q13 ||EMS1 || ||-CTTN and Oral Cavity Cancer || 11|
|ALDH2 ||12q24.2 ||ALDM, ALDHI, ALDH-E2 || ||-ALDH2 and Oral Cavity Cancer || 10|
|TWIST1 ||7p21.2 ||CRS, CSO, SCS, ACS3, CRS1, BPES2, BPES3, TWIST, bHLHa38 || ||-TWIST1 and Oral Squamous Cell Carcinoma || 10|
|PDPN ||1p36.21 ||T1A, GP36, GP40, Gp38, OTS8, T1A2, TI1A, T1A-2, AGGRUS, HT1A-1, PA2.26 || ||-PDPN and Oral Cavity Cancer || 9|
|ADH1C ||4q23 ||ADH3 || ||-ADH1C and Oral Cavity Cancer || 8|
|ABCG2 ||4q22 ||MRX, MXR, ABCP, BCRP, BMDP, MXR1, ABC15, BCRP1, CD338, GOUT1, CDw338, UAQTL1, EST157481 || ||-ABCG2 and Oral Cavity Cancer || 8|
|EDNRB ||13q22 ||ETB, ET-B, ETB1, ETBR, ETRB, HSCR, WS4A, ABCDS, ET-BR, HSCR2 || ||-EDNRB and Oral Cavity Cancer || 8|
|CDK2AP1 ||12q24.31 ||DOC1, ST19, DORC1, doc-1, p12DOC-1 || ||-CDK2AP1 and Oral Cavity Cancer || 7|
|AIDA ||1q41 ||C1orf80 || ||-AIDA and Oral Cavity Cancer || 6|
|LAMC2 ||1q25-q31 ||B2T, CSF, EBR2, BM600, EBR2A, LAMB2T, LAMNB2 || ||-LAMC2 and Oral Cavity Cancer || 6|
|MMP10 ||11q22.3 ||SL-2, STMY2 || ||-MMP10 and Oral Cavity Cancer || 5|
|KIAA1524 ||3q13.13 ||p90, CIP2A || ||-KIAA1524 and Oral Cavity Cancer || 4|
|FAT1 ||4q35 ||FAT, ME5, CDHF7, CDHR8, hFat1 || ||-FAT1 and Oral Cavity Cancer || 4|
|RPS6 ||9p21 ||S6 || ||-RPS6 and Oral Cavity Cancer || 4|
|IMP3 ||15q24 ||BRMS2, MRPS4, C15orf12 || ||-IMP3 and Oral Cavity Cancer || 3|
|ENDOU ||12q13.1 ||P11, PP11, PRSS26 || ||-ENDOU and Oral Cavity Cancer || 3|
|CSMD1 ||8p23.2 ||PPP1R24 || ||-CSMD1 and Oral Cavity Cancer || 3|
|MALL ||2q13 ||BENE || ||-MALL and Oral Cavity Cancer || 3|
|FGF19 ||11q13.1 || || ||-FGF19 and Oral Cavity Cancer || 3|
|THBS2 ||6q27 ||TSP2 || ||-THBS2 and Oral Cavity Cancer || 3|
|NTRK2 ||9q22.1 ||TRKB, trk-B, GP145-TrkB || ||-NTRK2 and Oral Cavity Cancer || 2|
|HOXC13 ||12q13.3 ||HOX3, ECTD9, HOX3G || ||-HOXC13 and Oral Cavity Cancer || 2|
|ING5 ||2q37.3 ||p28ING5 || ||-ING5 and Oral Cavity Cancer || 2|
|BCL2A1 ||15q24.3 ||GRS, ACC1, ACC2, BFL1, ACC-1, ACC-2, HBPA1, BCL2L5 || ||-BCL2A1 and Oral Cavity Cancer || 2|
|CFLAR ||2q33-q34 ||CASH, FLIP, MRIT, CLARP, FLAME, Casper, FLAME1, c-FLIP, FLAME-1, I-FLICE, c-FLIPL, c-FLIPR, c-FLIPS, CASP8AP1 || ||-CFLAR and Oral Cavity Cancer || 1|
|RXRB ||6p21.3 ||NR2B2, DAUDI6, RCoR-1, H-2RIIBP || ||-RXRB and Oral Cavity Cancer || 1|
|GHRH ||20q11.2 ||GRF, INN, GHRF || ||-GHRH and Oral Cavity Cancer || 1|
|BDNF ||11p13 ||ANON2, BULN2 || ||-BDNF and Oral Cavity Cancer || 1|
Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).
Hsieh R, Nico MM, Camillo CM, et al.Mutational Status of NRAS and BRAF Genes and Protein Expression Analysis in a Series of Primary Oral Mucosal Melanoma.
Am J Dermatopathol. 2017; 39(2):104-110 [PubMed
] Related Publications
Primary oral mucosal melanoma is an extremely rare and aggressive tumor arising from melanocytes located in the mucosal epithelium of the oral cavity. Although malignant melanoma of oral mucosa shares some clinical features with its cutaneous counterpart, it has been associated with a worst prognosis; its etiopathogenesis are still only partially unraveled as there is no influence of UV radiation. It is known that the mitogen-activated protein kinase pathway mediates cellular responses to growth signals and its activation is an important phenomenon in melanoma. The aim of this study was to evaluate NRAS and BRAF genes, both components of mitogen-activated protein kinase molecular pathway, and compare with their protein expression. Point mutations of NRAS (codons 12, 13, and 61) and BRAF (codon 600) were screened by pyrosequencing method, and its results were associated to the protein expression of RAS and BRAF performed by immunohistochemistry. The authors observed mutation in BRAF 600 (3/14), NRAS codons 12 and 13 (2/14), and NRAS codon 61 (2/8). One case showed positive RAS protein expression, but no mutation was observed. Twelve in 14 cases showed positive BRAF protein expression: 3 cases showed BRAF mutation; 2 cases showed NRAS codon 61 mutation; 2 cases showed NRAS codons 12 and 13 mutation but not simultaneously. Although NRAS and BRAF mutation frequency and RAS protein expression are low, BRAF protein expression was intense; probably, NRAS and BRAF mutations are independent events and alternative molecular mechanisms in the primary oral mucosal melanoma tumorigenesis.Related: Melanoma BRAF NRAS
Zhang CZLong non-coding RNA FTH1P3 facilitates oral squamous cell carcinoma progression by acting as a molecular sponge of miR-224-5p to modulate fizzled 5 expression.
Gene. 2017; 607:47-55 [PubMed
] Related Publications
A growing body of evidence has indicated that long non-coding RNAs (lncRNAs) function as competing endogenous RNAs (ceRNAs) during tumorigenesis. In this study, the qRT-PCR results revealed that the lncRNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) was over-expressed in oral squamous cell carcinoma (OSCC) and decreased the survival rate of OSCC patients. Ectopic expression of FTH1P3 facilitates cell proliferation and colony formation in OSCC cells. Moreover, FTH1P3 acted as a competitive endogenous RNA (ceRNA), effectively becoming sponge for miR-224-5p and thereby modulating the expression of fizzled 5. Importantly, expression analysis revealed that both FTH1P3 and fizzled 5 were up-regulated in OSCC cell lines and tissues, and over-expression of fizzled 5 also functioned as an oncogene in OSCC cells. Our data demonstrated FTH1P3 facilitated OSCC progression by acting as a molecular sponge of miR-224-5p to modulate fizzled 5 expression. Thus, targeting the ceRNA network referring FTH1P3 may be a therapeutic target for treatment of OSCC.Related: MicroRNAs
Otsuka Y, Sato H, Oikawa T, et al.High expression of EPB41L5, an integral component of the Arf6-driven mesenchymal program, correlates with poor prognosis of squamous cell carcinoma of the tongue.
Cell Commun Signal. 2016; 14(1):28 [PubMed
] Free Access to Full Article Related Publications
BACKGROUND: Squamous cell carcinoma of the tongue (tongue SCC) is a major subtype of head and neck squamous cell carcinoma (HNSCC), which is an intractable cancer under current therapeutics. ARF6 and its effector AMAP1 are often overexpressed in different types of cancers, such as breast cancer and renal cancer, and in these cancers, AMAP1 binds to EPB41L5 to promote invasion, metastasis, and drug resistance. EPB41L5 is a mesenchymal-specific protein, normally induced during epithelial-mesenchymal transition (EMT) to promote focal adhesion dynamics. Similarly to breast cancer and renal cancer, the acquisition of mesenchymal phenotypes is the key process that drives the malignancy of HNSCC. We previously showed that the overexpression of AMAP1 in tongue SCC is statistically correlated with the poor outcome of patients. In this study, we examined whether tongue SCC also expresses EPB41L5 at high levels.
RESULTS: Immunohistochemical staining of clinical specimens of tongue SCC demonstrated that high expression levels of EPB41L5 statistically correlate with poor disease-free survival and poor overall survival rates of patients. The tongue SCC cell line SCC-9, which overexpress Arf6 and AMAP1, also expressed EPB41L5 at high levels to promote invasiveness, whereas the weakly invasive SCC-25 cells did not express EPB41L5 at notable levels. Among the different EMT-associated transcriptional factors, ZEB1 was previously found to be most crucial in inducing EPB41L5 in breast cancer and renal cancer. In contrast, expression levels of ZEB1 did not correlate with the expression levels of EPB41L5 in tongue SCC, whereas KLF8 and FOXO3 levels showed positive correlations with EPB41L5 levels. Moreover, silencing of EPB41L5 only marginally improved the drug resistance of SCC-9 cells, even when coupled with ionizing radiation.
CONCLUSION: Our results indicate that activation of the cancer mesenchymal program in tongue SCC, which leads to EPB41L5 expression, closely correlates with the poor prognosis of patients. However, ZEB1 was not the major inducer of EPB41L5 in tongue SCC, unlike in breast cancer and renal cancer. Thus, processes that trigger the mesenchymal program of tongue SCC, which drives their malignancies, seem to be substantially different from those of other cancers.
Inhibitor of DNA-binding (ID) proteins are negative regulators of basic helix-loop-helix transcription factors that generally stimulate cell proliferation and inhibit differentiation. However, the role of ID2 in cancer progression remains ambiguous. Here, we investigated the function of ID2 in ID2-null oral squamous cell carcinoma (OSCC) cells.MATERIALS AND METHODS:
We introduced an ID2 cDNA construct into ID2-null OSCC cells and compared them with empty-vector-transfected cells in terms of cell proliferation, invasion, and activity and expression of matrix metalloproteinase (MMP).RESULTS:
ID2 introduction resulted in enhanced malignant phenotypes. The ID2-expressing cells showed increased N-cadherin, vimentin, and E-cadherin expression and epithelial-mesenchymal transition. In addition, cell invasion drastically increased with increased expression and activity of MMP2. Immunoprecipitation revealed a direct interaction between ID2 and zinc finger transcription factor, snail family transcriptional repressor 1 (SNAIL1).CONCLUSION:
ID2 expression triggered a malignant phenotype, especially of invasive properties, through the ID2-SNAIL axis. Thus, ID2 represents a potential therapeutic target for OSCC.Related: ID2 MMP2 Signal Transduction
Revathidevi S, Manikandan M, Rao AK, et al.Analysis of APOBEC3A/3B germline deletion polymorphism in breast, cervical and oral cancers from South India and its impact on miRNA regulation.
Tumour Biol. 2016; 37(9):11983-11990 [PubMed
] Related Publications
Chattopadhyay E, De Sarkar N, Singh R, et al.Genome-wide mitochondrial DNA sequence variations and lower expression of OXPHOS genes predict mitochondrial dysfunction in oral cancer tissue.
Tumour Biol. 2016; 37(9):11861-11871 [PubMed
] Related Publications
Several studies reported that mtDNA mutations may play important roles in carcinogenesis although the mechanism is not clear yet. Most of the studies compared mtDNA sequences in a tumor with those in normal tissues from different individuals ignoring inter-individual variations. In this study, 271 SNPs, 7 novel SNPs (or SNVs), and 15 somatic mutations were detected in mtDNA of 8 oral cancer tissues with respect to reference (rCRS) and adjacent normal tissues, respectively, using Ion PGM next generation sequencing method. Most of the sequence variations (76 SNPs and 1 somatic) are present in D-loop region followed by CyB (36 SNPs), ATP6 (24 SNPs), ND5 (17 SNPs and 5 somatic), ND4 (18 coding and 2 somatic) and other non-coding and coding DNA sequences. A total of 53 and 8 non-synonymous SNPs and somatic mutations, respectively, were detected in tumor tissues and some of these variations may have deleterious effects on the protein function as predicted by bioinformatic analysis. Moreover, significantly low mtDNA contents and expression of several mitochondrial genes in tumor compared to adjacent normal tissues may have also affected mitochondrial functions. Taken together, this study suggests that mtDNA mutations as well as low expression of mtDNA coded genes may play important roles in tumor growth. Although the sample size is low, an important aspect of the study is the use of adjacent control tissues to find out somatic mutations and a change in the expression of mitochondrial genes, to rule out inter-individual and inter-tissue variations which are important issues in the study of mitochondrial genomics.Related: Mitochondrial DNA Mitochondrial Mutations in Cancer
Pramanik KK, Singh AK, Alam M, et al.Reversion-inducing cysteine-rich protein with Kazal motifs and its regulation by glycogen synthase kinase 3 signaling in oral cancer.
Tumour Biol. 2016; 37(11):15253-15264 [PubMed
] Related Publications
The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and glycogen synthase kinase (GSK3) are novel tumor suppressors, and emerging evidence has suggested their active role in oral cancer pathogenesis. In the present study, 112 human samples, including 55 fresh samples of 14 adjacent normal tissues, 25 noninvasive oral tumors, and 18 invasive tumors, were included. The messenger RNA (mRNA) expression, protein expression, and promoter methylation of the RECK gene, as well as the expression of GSK3β, phospho/total β-catenin, and c-myc, were measured by RT-PCR, bisulphate modification-PCR, immunohistochemistry, and Western blot analysis. Additionally, ectopic expression of in/active GSK3β was performed in cell culture experiments. This study provided information on the progressive silencing of RECK gene expression at the protein and mRNA levels paralleled with promoter hypermethylation at various stages of oral tumor invasion. RECK expression and the hypermethylation of the RECK gene promoter were negatively and positively correlated with pS(9)GSK3β/c-myc expression, respectively. Further, a negative trend of RECK protein expression with nuclear β-catenin expression was observed. Induced expression of active GSK3β reversed the RECK silencing in SCC9 cells. Collectively, our results demonstrated that the silencing of the RECK gene, possibly regulated by the GSK3β pathway, is an important event in oral cancer invasion and this pathway could be exploited for therapeutic interventions.Related: RECK
Multani S, Saranath DGenotypic distribution of single nucleotide polymorphisms in oral cancer: global scene.
Tumour Biol. 2016; 37(11):14501-14512 [PubMed
] Related Publications
Globocan 2012 reports the global oral cancer incidence of 300,373 new oral cancer cases annually, contributing to 2.1 % of the world cancer burden. The major well-established risk factors for oral cancer include tobacco, betel/areca nut, alcohol and high-risk oncogenic human papilloma virus (HPV) 16/18. However, only 5-10 % of individuals with high-risk lifestyle develop oral cancer. Thus, genomic variants in individuals represented as single nucleotide polymorphisms (SNPs) influence susceptibility to oral cancer. With a view to understanding the role of genomic variants in oral cancer, we reviewed SNPs in case-control studies with a minimum of 100 cases and 100 controls. PubMed and HuGE navigator search engines were used to obtain data published from 1990 to 2015, which identified 67 articles investigating the role of SNPs in oral cancer. Single publications reported 93 SNPs in 55 genes, with 34 SNPs associated with a risk of oral cancer. Meta-analysis of data in multiple studies defined nine SNPs associated with a risk of oral cancer. The genes were associated with critical functions deregulated in cancers, including cell proliferation, immune function, inflammation, transcription, DNA repair and xenobiotic metabolism.
Anil S, Gopikrishnan PB, Basheer AB, et al.Association of Poly (ADP-Ribose) Polymerase 1 Variants with Oral Squamous Cell Carcinoma Susceptibility in a South Indian Population.
Asian Pac J Cancer Prev. 2016; 17(8):4107-11 [PubMed
] Related Publications
Oral cancers account for approximately 2% of all cancers diagnosed each year; however, the vast majority (80%) of the affected individuals are smokers whose risk of developing a lesion is five to nine times greater than that of non-smokers. Tobacco smoke contains numerous carcinogens that cause DNA damage, including oxidative lesions that are removed effectively by the base-excision repair (BER) pathway, in which poly (ADP-ribose) polymerase 1 (PARP-1), plays key roles. Genetic variations in the genes encoding DNA repair enzymes may alter their functions. Several studies reported mixed effects on the association between PARP-1 variants and the risk of cancer development. Till now no reported studies have investigated the association between PARP-1 variants and oral squamous cell carcinoma (OSCC) risk in an Indian population.MATERIALS AND METHODS:
In the present case control study 100 OSCC patients and 100 matched controls were genotyped using PARP1 single nucleotide peptides (SNP's) rs1136410 and rs3219090 using TaqMan assays.RESULTS:
The results indicated significantly higher risk with PARP1 rs1136410 minor allele "C" (OR=1.909; p=0.02942; CI, 1.060- 3.439). SNP rs1136410 also showed significantly increased risk in patients with smoking habit at C/C genotype and at minor allele C.CONCLUSIONS:
The PAPR-1 Ala762Val polymorphism may play a role in progression of OSCC. Larger studies with a greater number of samples are needed to verify these findings.Related: PARP1
Patel S, Rawal RRole of miRNA dynamics and cytokine profile in governing CD44v6/Nanog/PTEN axis in oral cancer: modulating the master regulators.
Tumour Biol. 2016; 37(11):14565-14575 [PubMed
] Related Publications
Late diagnosis, low therapeutic response, and metastasis are accountable for poor 5-year survival rate of OSCC. These failures are attributed to the existence of "cancer stem cell (CSC)" subpopulation. Hence, it is necessary to identify and understand the mechanism of CSCs in tumor development, metastasis, and chemotherapeutic response. Propelling evidences suggest that microRNA (miRNA)-mediated regulation and cytokines of tumor microenvironment have the ability to modulate CSC signalling pathway; however, their exact mechanism needs to be elucidated. Thus, in this study, we characterized CSC markers and highlighted the miRNA dynamics and cytokine profile regulating these CSCs in a pathway-dependent manner. Our results demonstrated CD44+ subpopulation as tumor-initiating cells with self-renewal capability, tumorigenic growth potential and intrinsic chemoresistance. These tumors exhibited increased expression of CSC markers (CD44v3, CD44v6, Nanog, and Bmi1) and significantly reduced expression of PTEN and ATM in OSCC patients. Pathway analysis of these CSC markers demonstrated a prospective pathway regulated by miRNA and cytokine network. On analyzing these modulators, we observed decreased expression of miRNA542-3p, miRNA34a and miRNA9, and significant upregulation of miRNA21, thus forming an unexplored axis. Cytokine profiling revealed significantly increased levels of IL-6 and IL-8 compared to normals and demonstrated their strong association with CD44v6. Collectively, this study indicates that miR5423p and miR34a targets the CD44v6-Nanog-PTEN axis, thus playing a vital role in regulating the CSC properties. Furthermore, we speculate an impinging role of cytokines IL-6 and IL-8 in regulating this CSC-mediated pathway which can have prognostic and therapeutic implications.Related: MicroRNAs PTEN IL6 microRNA mir-21 NANOG
Selenium-binding protein 1 (SELENBP1) expression is reduced markedly in many types of cancers and low SELENBP1 expression levels are associated with poor patient prognosis.METHODS:
SELENBP1 gene expression in head and neck squamous cell carcinoma (HNSCC) was analyzed with GEO dataset and characteristics of SELENBP1 expression in paraffin embedded tissue were summarized. Expression of SELENBP1 in nasopharyngeal carcinoma (NPC), laryngeal cancer, oral cancer, tonsil cancer, hypopharyngeal cancer and normal tissues were detected using immunohistochemistry, at last, 99 NPC patients were followed up more than 5 years and were analyzed the prognostic significance of SELENBP1.RESULTS:
Analysis of GEO dataset concluded that SELENBP1 gene expression in HNSCC was lower than that in normal tissue (P < 0.01), but there was no significant difference of SELENBP1 gene expression in different T-stage and N-stage (P > 0.05). Analysis of pathological section concluded that SELENBP1 in the majority of HNSCC is low expression and in cancer nests is lower expression than surrounding normal tissue, even associated with the malignant degree of tumor. Further study indicated the low SELENBP1 expression group of patients with NPC accompanied by poor overall survival and has significantly different comparing with the high expression group.CONCLUSION:
SELENBP1 expression was down-regulated in HNSCC, but has no associated with T-stage and N-stage of tumor. Low expression of SELENBP1 in patients with NPC has poor over survival, so SELENBP1 could be a novel biomarker for predicting prognosis.Related: Hypopharyngeal Cancer Cancer of the Larynx Laryngeal Cancer - Molecular Biology Nasopharyngeal Cancer
Sun L, Liang J, Wang Q, et al.MicroRNA-137 suppresses tongue squamous carcinoma cell proliferation, migration and invasion.
Cell Prolif. 2016; 49(5):628-35 [PubMed
] Related Publications
Tongue squamous cell carcinoma (TSCC) is the most frequent type of oral malignancy. Increasing evidence has shown that miRNAs play key roles in many biological processes such as cell development, invasion, proliferation, differentiation, metabolism, apoptosis and migration.MATERIALS AND METHODS:
qRT-PCR analysis was performed to measure miR-137 expression. CCK-8 analysis, cell colony formation, wound-healing analysis and invasion were performed to detect resultant cell functions. The direct target of miR-137 was labelled and measured by luciferase assay and Western blotting.RESULTS:
We demonstrated that expression of miR-137 was downregulated in TSCC tissues compared to matched normal ones. miR-137 expression was downregulated in TSCC lines (SCC4, SCC1, UM1 and Cal27) compared to the immortalized NOK16B cell line and normal oral keratinocytes in culture (NHOK). In addition, we have shown that miR-137 expression was epigenetically regulated in TSCCs. Overexpression of miR-137 suppressed TSCC proliferation and colony formation. Ectopic expression of miR-137 promoted expression of the epithelial biomarker, E-cadherin, and inhibited the mesenchymal biomarker, N-cadherin, as well as vimentin and Snail expression, indicating that miR-137 suppressed TSCC epithelial-mesenchymal transition (EMT). We also showed that ectopic expression of miR-137 inhibited TSCC invasion and migration. In addition, we identified SP1 as a direct target gene of miR-137 in SCC1 cells. SP1 overexpression rescued inhibitory effects exerted by miR-137 on cell proliferation and EMT.CONCLUSIONS:
These results indicate that miR-137 acted as a tumour suppressor in TSCC by targeting SP1.Related: MicroRNAs
Radunovic M, Nikolic N, Milenkovic S, et al.The MMP-2 and MMP-9 promoter polymorphisms and susceptibility to salivary gland cancer.
J BUON. 2016 May-Jun; 21(3):597-602 [PubMed
] Related Publications
Matrix metalloproteinases (MMPs) are a family of endopeptidases that may play an important role in the development of salivary gland cancer (SGC). MMP-2 and MMP-9, members of the gelatinase protein family, are capable of degrading type IV collagen of basement membranes, and their overexpression is often associated with tumor aggressiveness and poor prognosis. The aim of this study was to establish the role of single nucleotide polymorphisms (SNPs) in MMP-2 and MMP-9 genes as putative susceptibility factors for the development of SGC.METHODS:
The MMP-2 -1306 C>T, MMP-2 -1575 G>A and MMP-9 -1562 C>T polymorphisms were analyzed in 93 SGC cases and 100 controls using PCR-RFLP.RESULTS:
The T allele for the MMP-2-1306 C>T polymorphism exhibited its effect in heterozygous carriers, increasing the risk for SGC (odds ratio/OR 1.98, 95% CI 1.07-3.65, p=0.03). According to the dominant model, CT+TT genotypes had a 2-fold increased risk of developing SGCs (p=0.02).When the dominant model was applied for the MMP2 -1575 G>A, individuals with GA+AA genotypes exhibited a 1.77-fold increase in cancer risk, but with borderline significance (p=0.049). Heterozygous carriers of the variant T allele for the MMP-9 -1562 C>T polymorphism had roughly a 2-fold increase in susceptibility for SGC compared to wild type homozygotes (CC) (p=0.02).CONCLUSION:
Our findings suggest MMP-2-1306 C>T and MMP-9-1562 C>T polymorphisms genotypes seem to influence the development of SGCs, whereas MMP-2 -1575 G>A seems to be of a minor importance.Related: MMP2 MMP9: matrix metallopeptidase 9 Salivary Gland Cancer
With the development of functional genomics studies, a mass of long non-coding RNAs (LncRNA) were discovered from the human genome. Long non-coding RNAs serve as pivotal regulators of genes that are able to generate LncRNA-binding protein complexes to modulate a great number of genes. Recently, the LncRNA urothelial carcinoma-associated 1 (UCA1) has been revealed to be dysregulated, which plays a critical role in the development of a few cancers. However, the role of the biology and clinical significance of UCA1 in the tumorigenesis of oral squamous cell carcinoma (OSCC) remain unknown. We found that UCA1 expression levels were upregulated aberrantly in tongue squamous cell carcinoma tissues and associated with lymph node metastasis and TNM stage. We explored the expression, function, and molecular mechanism of LncRNA UCA1 in OSCC. In the present work, we revealed that UCA1 silencing suppressed proliferation and metastasis and induced apoptosis of OSCC cell lines in vitro and in vivo, which might be related to the activation level of the WNT/β-catenin signaling pathway. Our research results emphasize the pivotal role of UCA1 in the oncogenesis of OSCC and reveal a novel LncRNA UCA1-β-catenin-WNT signaling pathway regulatory network that could contribute to our understanding in the pathogenesis of OSCC and assist in the discovery of a viable LncRNA-directed diagnostic and therapeutic strategy for this fatal disease.Related: Apoptosis CTNNB1
Govindarajan GV, Bhanumurthy L, Balasubramanian A, Ramanathan AA Novel Mutation in the DNA Binding Domain of NFKB is Associated with Speckled Leukoplakia.
Asian Pac J Cancer Prev. 2016; 17(7):3627-9 [PubMed
] Related Publications
BACKGROUND: Activation and inactivation of nuclear factor of kappa light chain gene enhancer in B cells (NFKB) is tightly regulated to ensure effective onset and cessation of defensive inflammatory signaling. However, mutations within NFKB, or change in activation and inactivation molecules have been reported in a few cancers. Although oral squamous cell carcinoma is one of the most prevalent forms of cancer in India, with a development associated with malignant transformation of precancerous lesions, the genetic status of NFKB and relative rates of change in oral precancerous lesions remain unknown. Hence in the present study we investigated all twenty four exons of NFKB gene in two precancerous lesions, namely oral submucous fibrosis (OSMF) and oral leukoplakia (OL) to understand its occurrence, incidence and assess its possible contribution to malignant transformation.
MATERIALS AND METHODS: Chromosomal DNA isolated from twenty five each of OSMF and OL tissue biopsy samples were subjected to PCR amplification with intronic primers flanking twenty four exons of the NFKB gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status.
RESULTS: Sequence analysis identified a novel heterozygous mutation, c.419T>A causing substitution of leucine with glutamine at codon 140 (L140Q) in an OL sample.
CONCLUSIONS: The identification of a substitution mutation L140Q within the DNA binding domain of NFKB in OL suggests that NFKB mutation may be relatively an early event during transformation. To the best of our knowledge, this study is the first to have identified a missense mutation in NFKB in OL.
Ribeiro IP, Caramelo F, Marques F, et al.WT1, MSH6, GATA5 and PAX5 as epigenetic oral squamous cell carcinoma biomarkers - a short report.
Cell Oncol (Dordr). 2016; 39(6):573-582 [PubMed
] Related Publications
Oral squamous cell carcinoma (OSCC) is a frequently occurring aggressive malignancy with a heterogeneous clinical behavior. Based on the paucity of specific early diagnostic and prognostic biomarkers, which hampers the appropriate treatment and, ultimately the development of novel targeted therapies, we aimed at identifying such biomarkers through a genetic and epigenetic analysis of these tumors.METHODS:
93 primary OSCCs were subjected to DNA copy number alteration (CNA) and methylation status analyses using methylation-specific multiplex ligation-dependent probe amplification (MS-MPLA). The genetic and epigenetic OSCC profiles obtained were associated with the patients' clinic-pathological features.RESULTS:
We found that WT1 gene promoter methylation is a predictor of a better prognosis and that MSH6 and GATA5 gene promoter methylation serve as predictors of a worse prognosis. GATA5 gene promoter methylation was found to be significantly associated with a shorter survival rate. In addition, we found that PAX5 gene promoter methylation was significantly associated with tongue tumors. To the best of our knowledge, this is the first study that highlights this specific set of genes as epigenetic diagnostic and prognostic biomarkers in OSCC.CONCLUSIONS:
Our data highlight the importance of epigenetically assessing OSCCs to identify key genes that may serve as diagnostic and prognostic biomarkers and, potentially, as candidate therapeutic targets.Related: WT1 MSH6
Wang X, Li F, Zhou XmiR-204-5p regulates cell proliferation and metastasis through inhibiting CXCR4 expression in OSCC.
Biomed Pharmacother. 2016; 82:202-7 [PubMed
] Related Publications
MicroRNAs (miRNAs) are important small molecules in cancer including oral squamous cell carcinoma (OSCC) which regulate gene expression at post-transcriptional levels. MiR-204-5p acts as a tumor suppressor in some of cancers, but the role of it in OSCC is not known. The aim of this study is to investigate the expression and functional roles of miR-204-5p in OSCC. The results showed that the expression of miR-204-5p was lower in cancer tissues or cells. Next, cell proliferation, cell cycle, migration and invasion were detected. It was found that miR-204-5p could enhance OSCC cell proliferation and metastasis. MiR-204-5p was predicted as a regulatory miRNA of CXCR4 in OSCC, and the data analysis indicated that there was a negatively relationship between miR-204-5p and CXCR4 expression in OSCC tissues from the patients. In a conclusion, our findings suggested that miR-204-5p may function as an inhibitory RNA molecule in OSCC by targeting CXCR4.Related: MicroRNAs CXCR4
Mays AC, Feng X, Browne JD, Sullivan CAChemokine and Chemokine Receptor Profiles in Metastatic Salivary Adenoid Cystic Carcinoma.
Anticancer Res. 2016; 36(8):4013-8 [PubMed
] Related Publications
To characterize the chemokine pattern in metastatic salivary adenoid cystic carcinoma (SACC).MATERIALS AND METHODS:
Real-time polymerase chain reaction (RT-PCR) was used to compare chemokine and chemokine receptor gene expression in two SACC cell lines: SACC-83 and SACC-LM (lung metastasis). Chemokines and receptor genes were then screened and their expression pattern characterized in human tissue samples of non-recurrent SACC and recurrent SACC with perineural invasion.RESULTS:
Expression of chemokine receptors C5AR1, CCR1, CCR3, CCR6, CCR7, CCR9, CCR10, CXCR4, CXCR6, CXCR7, CCRL1 and CCRL2 were higher in SACC-83 compared to SACC-LM. CCRL1, CCBP2, CMKLR1, XCR1 and CXCR2 and 6 chemokine genes (CCL13, CCL27, CXCL14, CMTM1, CMTM2, CKLF) were more highly expressed in tissues of patients without tumor recurrence/perineural invasion compared to those with tumor recurrence. CCRL1 (receptor), CCL27, CMTM1, CMTM2, and CKLF (chemokine) genes were more highly expressed in SACC-83 and human tissues of patients without tumor recurrence/perineural invasion.CONCLUSION:
CCRL1, CCL27, CMTM1, CMTM2 and CKLF may play important roles in the development of tumor metastases in SACC.Related: Salivary Gland Cancer
Sumida T, Kamata YU, Kobayashi Y, et al.ID1 Controls Aggressiveness of Salivary Gland Cancer Cells via Crosstalk of IGF and AKT Pathways.
Anticancer Res. 2016; 36(8):3865-70 [PubMed
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Inhibitor of differentiation or DNA binding 1 (ID1) is overexpressed in human salivary gland cancer (SGC). The insulin growth factor (IGF) system is an attractive target in cancer control because it is associated with various cancer progressions.MATERIALS AND METHODS:
The human SGC cell line HSY with abundant ID1 was used. ID1 knockdown and its effect on the IGF system were investigated. Cell proliferation and invasion, as well as associated protein expression, were analyzed. Phospho-AKT was also evaluated.RESULTS:
ID1 knockdown reduced cell proliferation and invasion, while the expression of proteins associated with malignant phenotypes was altered. IGF-II expression was suppressed, suggesting that this system is one of the mechanisms underlying effects of ID1 in SGC cells. c-Myc was up-regulated, whereas p21 and p27 were down-regulated. Moreover, phospho-AKT was reduced in ID1-knockeddown cells.CONCLUSION:
ID1 down-regulation induced parallel changes in the IGF and AKT pathways. The crosstalk of these pathways may enhance malignant phenotypes in SGCs.Related: IGF2 AKT1 Salivary Gland Cancer Signal Transduction MYC
Lee C, Ramos DMRegulation of Multicellular Spheroids by MAPK and FYN Kinase.
Anticancer Res. 2016; 36(8):3833-8 [PubMed
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BACKGROUND: DNA methylation profiling of heterogeneous head and neck squamous cell carcinoma (HNSCC) cohorts has been reported to predict patient outcome. We investigated if a prognostic DNA methylation profile could be found in tumour tissue from a single uniform subsite, the oral tongue. The methylation status of 109 comprehensively annotated oral tongue squamous cell carcinoma (OTSCC) formalin-fixed paraffin-embedded (FFPE) samples from a single institution were examined with the Illumina HumanMethylation450K (HM450K) array. Data pre-processing, quality control and analysis were performed using R packages. Probes mapping to SNPs, sex chromosomes and unreliable probes were accounted for prior to downstream analyses. The relationship between methylation and patient survival was examined using both agnostic approaches and feature selection. The cohort was enlarged by incorporation of 331 The Cancer Genome Atlas (TCGA) HNSCC samples, which included 91 TCGA OTSCC samples with HM450K and survival data available.
RESULTS: Given the use of FFPE-derived DNA, we defined different cohorts for separate analyses. Overall, similar results were found between cohorts. With an unsupervised approach, no distinct hypermethylated group of samples was identified and nor was a prognostic methylation profile identified. The use of multiple downstream feature selection approaches, including a linear models for microarray data (LIMMA), centroid feature selection (CFS), and recursive feature elimination (RFE) support vector machines, similarly failed to identify a significant methylation signature informative for patient prognosis or any clinicopathological data available. Furthermore, we were unable to confirm the prognostic methylation profiles or specific prognostic loci reported within the literature for HNSCC.
CONCLUSIONS: With genome-scale assessment of DNA methylation using HM450K in one of the largest OTSCC cohorts to date, we were unable to identify a hypermethylated group of tumours or a prognostic methylation signature. This suggests that either DNA methylation in isolation is not likely to be of prognostic value or larger cohorts are required to identify such a biomarker for OTSCC.
Peng X, McCormick DLIdentification of reliable reference genes for quantitative gene expression studies in oral squamous cell carcinomas compared to adjacent normal tissues in the F344 rat model.
Oncol Rep. 2016; 36(2):1076-84 [PubMed
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Oral squamous cell carcinomas (OSCCs) induced in F344 rats by 4-nitroquinoline-1-oxide (4-NQO) demonstrate considerable phenotypic similarity to human oral cancers and the model has been widely used for carcinogenesis and chemoprevention studies. Molecular characterization of this model needs reliable reference genes (RGs) to avoid false- positive and -negative results for proper interpretation of gene expression data between tumor and adjacent normal tissues. Microarray analysis of 11 pairs of OSCC and site-matched phenotypically normal oral tissues from 4-NQO-treated rats identified 10 stably expressed genes in OSCC compared to adjacent normal tissues (p>0.5, CV<15%) that could serve as potential RGs in this model. The commonly used 27 RGs in the rat were also analyzed based on microarray data and most of them were found unsuitable for RGs in this model. Traditional RGs such as ACTB and GAPDH were significantly altered in OSCC compared to adjacent normal tissues (p<0.01, n=11); however, the Hsp90ab1 was ranked as the best RG candidate and the combination of Hsp90ab1 and HPRT1 was identified by NormFinder to be a superior reference for gene normalization among the commonly used RGs. This result was also validated by RT-PCR based on the selected top RG candidate pool. These data suggest that there are no common RGs suitable for different models and RG(s) should be identified before gene expression analysis. We successfully identified Hsp90ab1 as a stable RG in 4-NQO-induced OSCC compared to adjacent normal tissues in F344 rats. The combination of two stably expressed genes may be a better option for gene normalization in tissue samples.
Irimie AI, Braicu C, Pileczki V, et al.Knocking down of p53 triggers apoptosis and autophagy, concomitantly with inhibition of migration on SSC-4 oral squamous carcinoma cells.
Mol Cell Biochem. 2016; 419(1-2):75-82 [PubMed
] Related Publications
Oral squamous cell carcinoma (OSCC) is a malignancy with elevated prevalence and somber prognosis due to the fact that most of the patients are diagnosed at an advanced stage. p53 has a crucial role in proliferation and apoptosis during the occurrence and development of numerous malignant tumors. The impact of mutated p53 on the development and progression of OSCC is unclear and might have therapeutic implications. Using an in vitro RNA interference experiment, we have evaluated the impact of p53 knockdown on cell viability, apoptosis, migration, and gene expression for key genes involved in apoptosis and angiogenesis. We observed that inhibiting the expression of p53 decreased the proliferation ability and induced apoptosis/autophagy in SSC-4 cells. Moreover, we observed that this has decreased migration and has blocked the expression of VEGF. In conclusion, our research provides a proof that a direct connection between p53 knockdown and OSCC cell death can be established, therefore opening new potential directions in OSCC molecular therapeutics and management.Related: Apoptosis TP53
Sumida T, Ishikawa A, Nakano H, et al.Targeting ID2 expression triggers a more differentiated phenotype and reduces aggressiveness in human salivary gland cancer cells.
Genes Cells. 2016; 21(8):915-20 [PubMed
] Related Publications
Inhibitors of DNA-binding (ID) proteins are negative regulators of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. We previously determined that ID1 was highly expressed in aggressive salivary gland cancer (SGC) cells in culture. Here, we show that ID2 is also expressed in aggressive SGC cells. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N-cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. Moreover, ID2 knockdown almost completely suppresses invasion and the expression of matrix metalloproteinase 9. In conclusion, ID2 expression maintains an aggressive phenotype in SGC cells, and ID2 repression triggers a reduction in cell aggressiveness. ID2 therefore represents a potential therapeutic target during SGC progression. ID proteins are negative regulators of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N-cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. ID2 therefore represents a potential therapeutic target during SGC progression.Related: ID2 Salivary Gland Cancer
Kil TJ, Kim HS, Kim HJ, et al.Genetic Abnormalities in Oral Leukoplakia and Oral Cancer Progression.
Asian Pac J Cancer Prev. 2016; 17(6):3001-6 [PubMed
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BACKGROUND: The cancer progression of oral leukoplakia is an important watchpoint in the follow-up observation of the patients. However, potential malignancies of oral leukoplakia cannot be estimated by histopathologic assessment alone. We evaluated genetic abnormalities at the level of copy number variation (CNV) to investigate the risk for developing cancer in oral leukoplakias.
MATERIALS AND METHODS: The current study used 27 oral leukoplakias with histological evidence of dysplasia. The first group (progressing dysplasia) consisted of 7 oral lesions from patients with later progression to cancer at the same site. The other group (non- progressing dysplasia) consisted of 20 lesions from patients with no occurrence of oral cancer and longitudinal follow up (>7 years). We extracted DNA from Formalin-Fixed Paraffin-Embedded (FFPE) samples and examined chromosomal loci and frequencies of CNVs using Taqman copy number assays.
RESULTS: CNV frequently occurred at 3p, 9p, and 13q loci in progressing dysplasia. Our results also indicate that CNV at multiple loci-in contrast to single locus occurrences-is characteristic of progressing dysplasia.
CONCLUSIONS: This study suggests that genetic abnormalities of the true precancer demonstrate the progression risk which cannot be delineated by current histopathologic diagnosis.
Zhao J, Hu C, Chi J, et al.miR-24 promotes the proliferation, migration and invasion in human tongue squamous cell carcinoma by targeting FBXW7.
Oncol Rep. 2016; 36(2):1143-9 [PubMed
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Recent studies suggest that aberrant expression of miR-24 is linked to various human cancers, including tongue squamous cell carcinoma (TSCC). F-box and WD-40 domain protein 7 (FBXW7), a tumor-suppressor gene, is responsible for the degradation of several proto-oncogenes. However, the function and mechanism of miR-24 and FBXW7 in TSCC remains unclear. In the present study, we found that miR-24 was increased in TSCC tissues and cell lines, and that upregulation of miR-24 was associated with advanced clinical stage and a shorter overall survival of TSCC patients. Inhibition of miR-24 significantly suppressed the proliferation, migration and invasion of TSCC cells in vitro. Furthermore, miR-24 repressed FBXW7 expression by directly binding to the 3-untranslated region of FBXW7. Moreover, the suppression of FBXW7 increased the proliferation, migration and invasion of TSCC cells, and the restoration of FBXW7 substantially attenuated the oncogenic effects of miR-24. In conclusion, our results demonstrated that upregulation of miR-24 was associated with tumor progression and poor prognosis in TSCC patients, and that overexpression of miR-24 was correlated with the proliferation, migration and invasion of TSCC cells in vitro, at least partially through regulation of its functional target FBXW7. Thus, miR-24 may serve as a novel potential biomarker for the prognosis of TSCC patients.Related: MicroRNAs FBXW7
Xu JL, Xia R, Sun L, et al.Association of CYP1A1 MspI polymorphism with oral cancer risk in Asian populations: a meta-analysis.
Genet Mol Res. 2016; 15(2) [PubMed
] Related Publications
Numerous studies regarding the association between the CYP1A1 MspI polymorphism and oral cancer risk in Asian populations have shown controversial results. To get a more precise estimation of this relationship, we conducted a comprehensive meta-analysis. PubMed, the Cochrane Library, Elsevier Science Direct, Web of Knowledge, the Chinese National Knowledge Infrastructure, VIP, and Wan Fang Med Online were searched. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated using fixed-effects or random-effects models. Heterogeneity among studies was assessed using the Cochran Q test and I(2) statistics. Twelve articles including 1925 oral cancer patients and 2335 controls were ultimately included in the meta-analysis. Overall, the meta-analysis showed that the CYP1A1 MspI polymorphism was associated with oral cancer risk in Asians (m1/m1 vs m2/m2: OR = 0.46, 95%CI = 0.30-070, POR = 0.000; m1/m1 vs m1/m2+m2/m2: OR = 0.70, 95%CI = 0.51-0.98, POR = 0.037; m1/m1+m1/m2 vs m2/m2: OR = 0.48, 95%CI = 0.35-0.65, POR = 0.000). Subgroup analyses showed that the control source (hospital-based or population-based), the genotyping method [polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism], the country in which the study was conducted, and Hardy-Weinberg equilibrium (Yes or No) were positively related to the association. Sensitivity analysis suggested that the overall results showed no significant change in three genetic models when any one study was removed, and publication bias was undetected by the Egger test. The CYP1A1 MspI polymorphism may be associated with oral cancer risk in Asian populations.
Michailidou E, Tzimagiorgis G, Chatzopoulou F, et al.Salivary mRNA markers having the potential to detect oral squamous cell carcinoma segregated from oral leukoplakia with dysplasia.
Cancer Epidemiol. 2016; 43:112-8 [PubMed
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BACKGROUND: In the current study the presence of extracellular IL-1B, IL-8, OAZ and SAT mRNAs in the saliva was evaluated as a tool in the early detection of oral squamous cell carcinoma.
METHODS: 34 patients with primary oral squamous cell carcinoma stage T1N0M0/T2N0M0, 20 patients with oral leukoplakia and dysplasia (15 patients with mild dysplasia and 5 with severe dysplasia/in situ carcinoma) and 31 matched healthy-control subjects were included in the study. The presence of IL-1B, IL-8, OAZ and SAT mRNA was evaluated in extracellular RNA isolated from saliva samples using sequence-specific primers and real-time RT-PCR. ROC curve analysis was used to estimate the ability of the biomarkers to detect oral squamous cell carcinoma patients.
RESULTS: The data reveal that the combination of these four biomarkers provides a good predictive probability of up to 80% (AUC=0.799, p=0.002) for patients with oral squamous cell carcinoma but not patients suffering from oral leukoplakia with dysplasia. Moreover, the combination of only the two biomarkers (SAT and IL-8) also raises a high predictive ability of 75.5% (AUC=0.755, p=0.007) approximately equal to the four biomarkers suggesting the use of the two biomarkers only in the prediction model for oral squamous cell carcinoma patients limiting the economic and health cost in half.
CONCLUSION: SAT and IL-8 mRNAs are present in the saliva in high quality and quantity, with a good discriminatory ability for oral squamous cell carcinoma patients only but not for patients with oral leukoplakia and dysplasia an oral potentially malignant disorder.
The DNA mismatch repair (MMR) system is responsible for the detection and correction of errors created during DNA replication, thereby avoiding the incorporation of mutations in dividing cells. The prognostic value of alterations in MMR system has not previously been analyzed in oral squamous cell carcinoma (OSCC).The study comprised 115 cases of OSCC diagnosed between 1996 and 2010. The specimens collected were constructed into tissue microarray blocks. Immunohistochemical staining for MutSα complex proteins hMSH2 and hMSH6 was performed. The slides were subsequently scanned into high-resolution images, and nuclear staining of hMSH2 and hMSH6 was analyzed using the Nuclear V9 algorithm. Univariable and multivariable Cox proportional hazard regression models were performed to evaluate the prognostic value of hMSH2 and hMSH6 in OSCC.All cases in the present cohort were positive for hMSH2 and hMSH6 and a direct correlation was found between the expression of the proteins (P < 0.05). The mean number of positive cells for hMSH2 and hMSH6 was 64.44 ± 15.21 and 31.46 ± 22.38, respectively. These values were used as cutoff points to determine high protein expression. Cases with high expression of both proteins simultaneously were classified as having high MutSα complex expression. In the multivariable analysis, high expression of the MutSα complex was an independent prognostic factor for poor overall survival (hazard ratio: 2.75, P = 0.02).This study provides a first insight of the prognostic value of alterations in MMR system in OSCC. We found that MutSα complex may constitute a molecular marker for the poor prognosis of OSCC.
Yunoki T, Tabuchi Y, Hayashi A, Kondo TNetwork analysis of genes involved in the enhancement of hyperthermia sensitivity by the knockdown of BAG3 in human oral squamous cell carcinoma cells.
Int J Mol Med. 2016; 38(1):236-42 [PubMed
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BCL2-associated athanogene 3 (BAG3), a co-chaperone of the heat shock 70 kDa protein (HSPA) family of proteins, is a cytoprotective protein that acts against various stresses, including heat stress. The aim of the present study was to identify gene networks involved in the enhancement of hyperthermia (HT) sensitivity by the knockdown (KD) of BAG3 in human oral squamous cell carcinoma (OSCC) cells. Although a marked elevation in the protein expression of BAG3 was detected in human the OSCC HSC-3 cells exposed to HT at 44˚C for 90 min, its expression was almost completely suppressed in the cells transfected with small interfering RNA against BAG3 (siBAG) under normal and HT conditions. The silencing of BAG3 also enhanced the cell death that was increased in the HSC-3 cells by exposure to HT. Global gene expression analysis revealed many genes that were differentially expressed by >2-fold in the cells exposed to HT and transfected with siBAG. Moreover, Ingenuity® pathways analysis demonstrated two unique gene networks, designated as Pro-cell death and Anti-cell death, which were obtained from upregulated genes and were mainly associated with the biological functions of induction and the prevention of cell death, respectively. Of note, the expression levels of genes in the Pro-cell death and Anti-cell death gene networks were significantly elevated and reduced in the HT + BAG3-KD group compared to those in the HT control group, respectively. These results provide further insight into the molecular mechanisms involved in the enhancement of HT sensitivity by the silencing of BAG3 in human OSCC cells.