Research IndicatorsGraph generated 09 March 2017 using data from PubMed using criteria.
Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic. Tag cloud generated 09 March, 2017 using data from PubMed, MeSH and CancerIndex
Specific Cancers (5)
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).
OMIM, Johns Hopkin University
Referenced article focusing on the relationship between phenotype and genotype.
International Cancer Genome Consortium.
Summary of gene and mutations by cancer type from ICGC
Cancer Genome Anatomy Project, NCI
COSMIC, Sanger Institute
Somatic mutation information and related details
GEO Profiles, NCBI
Search the gene expression profiles from curated DataSets in the Gene Expression Omnibus (GEO) repository.
Latest Publications: MMP7 (cancer-related)
Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. In order to identify novel prognostic markers or therapeutic targets for CRC, we searched for candidate genes in our comprehensive gene expression libraries, and focused on SEC11A, which encodes the SPC18 protein. SPC18 plays a key role in the endoplasmic reticulum-Golgi secretory pathway and presumably regulates the secretion of various secretory proteins. An immunohistochemical analysis of SPC18 in 137 CRC tissue samples demonstrated that 79 (58%) CRC cases were positive for SPC18. SPC18-positive CRC cases were more advanced in terms of N classification (P = 0.0315) and tumor stage (P = 0.0240) than SPC18-negative CRC cases. Furthermore, the expression of SPC18 was an independent prognostic classifier for CRC patients. The cell growth and invasiveness of SPC18 siRNA-transfected CRC cell lines was less than that of the negative control siRNA-transfected cell lines. The levels of phosphorylated epidermal growth factor receptor, Erk and Akt were lower in SPC18 siRNA-transfected CRC cells than in control cells. The expression of SPC18 was colocalized with β-catenin nuclear localization and MMP7 at the invasive front. An immunohistochemical analysis of human colorectal polyp specimens revealed a sequential increase in the expression of SPC18 through the conventional adenoma-carcinoma pathway, while SPC18 was not expressed or was expressed to a lesser extent in serrated pathway-related tumors. These results suggest that SPC18 is involved in tumor progression, and is an independent prognostic classifier in patients with CRC.
Yu B, Liu X, Chang HMicroRNA-143 inhibits colorectal cancer cell proliferation by targeting MMP7.
Minerva Med. 2017; 108(1):13-19 [PubMed
] Related Publications
BACKGROUND: MicroRNAs (miRNAs) play critical roles in the development and progression of human malignancy. The levels of miR-143 microRNA are lower in malignant tumors - including colorectal cancer (CRC) - as it is a tumor suppressor. However, the potential mechanism of miR-143 in CRC remains largely unknown.
METHODS: Target prediction programs and luciferase reporter assay was used to predict the targets of miR-143. Following overexpression of miR-143 in CRC cells, target gene matrix metalloproteinase 7 (MMP7) expression was detected by quantitative real-time PCR (qRT-PCR) and western blot. In addition, the expression of MMP7 was quantified in CRC tissues and cell lines. Moreover, we determined the effect of MMP7 on CRC cell proliferation and invasion.
RESULTS: In the present study, TargetScan predicted that miR-143 could directly bind to 3'-UTR of MMP7 mRNA, and luciferase reporter assay further supported the hypothesis that MMP7 might act as a direct target gene of miR-143. Our data showed that increased expression of miR-143 repressed MMP7 expression in CRC cells both in mRNA and protein levels. Furthermore, qRT-PCR showed that the expression of MMP7 was increased in CRC tissues and cell lines, and inversely correlated with miR-143 expression in CRC tissues. Finally, our results indicated that increased expression of MMP7 reversed the potential influence of miR-143 on CRC cell proliferation and invasion ability.
CONCLUSIONS: Our results indicated that miR-143 might act as a tumor suppressor by targeting MMP7 during the development of CRC.
Rahman FU, Ali A, Khan IU, et al.Novel phenylenediamine bridged mixed ligands dimetallic square planner Pt(II) complex inhibits MMPs expression via p53 and caspase-dependent signaling and suppress cancer metastasis and invasion.
Eur J Med Chem. 2017; 125:1064-1075 [PubMed
] Related Publications
Novel phenylenediamine bridged mixed ligands dimetallic square planner Pt(II) complex (L-Pt-Py) was synthesized from simple commercially available precursors in good yield and characterized by (1)H, (13)C, 2D NOESY NMR and high resolution mass spectrometry (HR-ESI-MS). The stability of L-Pt-Py was checked by (1)H NMR in mixed DMSO-d6/D2O solvents. L-Pt-Py showed considerable in vitro cytotoxicity in lung (A549), breast (MCF-7) and liver (HepG2) cancer cell lines and strong in vivo growth inhibition in Escherichia coli (E. coli). These results were compared to the well-known market available platinum anticancer drug cisplatin. L-Pt-Py has strong ability to suppress the growth of multiple cancer cells. Mechanistically, it enhanced p53 protein expression and regulated p53-dependent genes expression such as p21, PUMA, MYC and hTERT. The TUNEL assay showed that L-Pt-Py induced cell death in cancer cells. Inhibition of caspase signaling with caspase inhibitor Z-VAD-FMK suggested that cell death induced by this complex was caspase-dependent. Importantly, L-Pt-Py has the ability to suppress the invasion and migration of human lung and luminal-like breast cancer cells. Similarly L-Pt-Py suppressed the expression of several matrix metalloproteinases (MMPs) such as MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9 to inhibit lung and breast cancer cell metastasis. L-Pt-Py showed stronger inhibitory effects on bacterial growth and also resulted in filamentous morphology of bacterial cells. The gel electrophoresis study of DNA migration revealed the strong interaction of L-Pt-Py with DNA. Taken altogether, L-Pt-Py was highly stable and the in vitro and in vivo biological study results corroborated this complex to be effective anticancer agent.
Li K, Ying M, Feng D, et al.Fructose-1,6-bisphosphatase is a novel regulator of Wnt/β-Catenin pathway in breast cancer.
Biomed Pharmacother. 2016; 84:1144-1149 [PubMed
] Related Publications
Fructose-1,6-bisphosphatase (FBP1), the rate-limiting enzyme in gluconeogenesis, is a tumor suppressor that frequently down-regulated in cancers, especially breast cancer. Here, we provide both supporting and contradicting evidences about the expression pattern and function of FBP1 in breast cancer. Data mining of Oncomine database showed that FBP1 is commonly up-regulated in tumor tissues compared with non-tumor tissues regardless of histological type. Analysis of a large-scale cohort derived from Kaplan-Meier Plotter showed that lower FBP1 expression associated with poor clinical outcome. Genetic silencing of FBP1 reduced aerobic glycolysis and the malignant potential of breast cancer cells. Gene set enrichment analysis (GSEA) of the expression profiles of breast cancer cells (n=59) revealed that cells exhibiting high expression of FBP1 had a lower activity of Wnt/β-Catenin pathway. FBP1 down-regulation enhanced the activity of Wnt/β-Catenin pathway and increased the level of its downstream targets, including c-Myc and MMP7. Collectively, our findings indicate that elevated FBP1 is a critical modulator in breast cancer progression by altering glucose metabolism and the activity of Wnt/β-Catenin pathway.
Li Z, Wei D, Yang C, et al.Overexpression of long noncoding RNA, NEAT1 promotes cell proliferation, invasion and migration in endometrial endometrioid adenocarcinoma.
Biomed Pharmacother. 2016; 84:244-251 [PubMed
] Related Publications
Long noncoding RNAs (lncRNAs) are emerging as important modulators in the biological processes and tumorigenesis. However, whether lncRNAs are involved in endometrial endometrioid adenocarcinoma (EEC) remains unclear. In the present study, we explored the expression pattern, clinical significance and biological function of nuclear enriched abundant transcript 1 (NEAT1) in EEC. The expression levels of NEAT1 were elevated in EEC tissues and cell lines, and higher expression levels of NEAT1 were positively correlated with FIGO stage and lymph node metastasis. Overexpression of NEAT1 in HEC-59 cells transfected with pGCMV-NEAT1 promotes cell growth, colony formation ability as well as invasive and migratory ability; while knock-down of NEAT1 in HEC-59 cells by siNEAT1 transfection exhibited the opposite effects. Flow cytometry analysis showed that overexpression of NEAT1 led to an increase in S-phase cells and attenuated cell apoptosis, and knock-down of NEAT1 induced G0/G1 arrest and also induced cell apoptosis in HEC-59 cells. Tumor metastasis real-time PRC array showed that six metastasis-related genes (c-myc, insulin like growth factor 1(IGF1), matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 7(MMP-7) were up-regulated, and Cadherin 1 and TIMP metallopeptidase inhibitor 2 were down-regulated) in NEAT1-overexpressing HEC-59 cells. Further qRT-PCR and western blot results confirmed that c-myc, IFG1, MMP-2 and MMP-7 were dys-regulated by NEAT1. Together, our data underscore the significance of NEAT1 in EEC development, and NEAT1 may a potential therapeutic target for EEC.
Yu L, Li X, Li H, et al.Rab11a sustains GSK3β/Wnt/β-catenin signaling to enhance cancer progression in pancreatic cancer.
Tumour Biol. 2016; 37(10):13821-13829 [PubMed
] Related Publications
The Rab family GTPases regulate many major biological processes during tumor progression such as cell proliferation, cytoskeleton organization, cell movement, and invasion. The present study aims to examine the clinical significance, biological roles, and molecular mechanism of Rab11a in pancreatic cancer progression. We examined expression pattern of Rab11a in 96 cases of pancreatic cancer specimens using immunohistochemistry and found Rab11a overexpression correlated with tumor-node-metastasis (TNM) stage (p = 0.0111). We depleted Rab11a in Bxpc3 cells using small interfering RNA (siRNA) and overexpressed Rab11a in Capan2 cells. Knockdown of Rab11a inhibited cell growth, invasion, and cell cycle progression while its overexpression facilitated cell growth, invasion, and cell cycle progression. In addition, Rab11a overexpression increased gemcitabine resistance and inhibited gemcitabine-induced apoptosis in Capan2 cells while its depletion reduced drug resistance. We investigated the role of Rab11a in the regulation of Wnt/β-catenin signaling and we demonstrated that Rab11a overexpression upregulated GSK3β phosphorylation and nuclear β-catenin accumulation. Rab11a depletion inhibited while its overexpression enhanced β-catenin/T-cell factor (TCF) transcriptional activity with corresponding change of Wnt target genes including cyclin D1, cyclin E, MMP7, and c-myc. Wnt inhibitor (FH535) partly attenuated the effects of Rab11a on cell proliferation and Wnt target genes. In conclusion, the present study demonstrated that Rab11a promotes aggressiveness of pancreatic cancer through GSK3β/Wnt/β-catenin signaling pathway.
Liu X, Chen Q, Hu XG, et al.PTP1B promotes aggressiveness of breast cancer cells by regulating PTEN but not EMT.
Tumour Biol. 2016; 37(10):13479-13487 [PubMed
] Related Publications
Metastasis is a complicated, multistep process and remains the major cause of cancer-related mortality. Exploring the molecular mechanisms underlying tumor metastasis is crucial for development of new strategies for cancer prevention and treatment. In this study, we found that protein tyrosine phosphatase 1B (PTP1B) promoted breast cancer metastasis by regulating phosphatase and tensin homolog (PTEN) but not epithelial-mesenchymal transition (EMT). By detecting PTP1B expression of the specimens from 128 breast cancer cases, we found that the level of PTP1B was higher in breast cancer tissues than the corresponding adjacent normal tissues. Notably, PTP1B was positively associated with lymph node metastasis (LNM) and estrogen receptor (ER) status. In vitro, disturbing PTP1B expression obviously attenuated cell migration and invasion. On the contrary, PTP1B overexpression significantly increased migration and invasion of breast cancer cells. Mechanistically, PTP1B knockdown upregulated PTEN, accompanied with an abatement of AKT phosphorylation and the expression of matrix metalloproteinase 2 (MMP2) and MMP7. Conversely, forced expression of PTP1B reduced PTEN and increased AKT phosphorylation as well as the expression of MMP2 and MMP7. Notably, neither EMT nor stemness of breast cancer cells was regulated by PTP1B. We also found that PTP1B acted as an independent prognostic factor and predicted poor prognosis in ER-positive breast cancer patients. Taken together, our findings provide advantageous evidence for the development of PTP1B as a potential therapeutic target for breast cancer, especially for ER-positive breast cancer patients.
Xiao XY, Lang XPCorrelation Between MMP-7 and bFGF Expressions in Non-small Cell Lung Cancer Tissue and Clinicopathologic Features.
Cell Biochem Biophys. 2015; 73(2):427-32 [PubMed
] Related Publications
The present study intends to investigate the correlation between clinicopathologic features of non-small cell lung cancer and matrix metalloproteinase-7 (MMP-7) and basic fibroblast growth factor (bFGF) and to investigate the roles of MMP-7 and bFGF in detecting the course of disease of non-small cell lung cancer. Ninety cases of paraffin-embedded tissue samples from patient with primary non-small cell lung cancer and fifty cases of lung tissue samples from normal subjects were included in the present study. Immunohistochemical S-P method was used to detect proteins MMP-7 and bFGF. (1) The positive rate of MMP-7 protein was 14 % in normal lung tissue section and 68.89 % in non-small cell lung cancer tissue section, and the difference was statistically significant (χ (2) = 38.774, P = 0.000 < 0.05). There were 43 cases (43/56) with positive expression in patients with squamous cell carcinoma and 22 cases (22/34) with positive expression in patients with adenocarcinoma, and the difference was not statistically significant (χ (2) = 1.539, P = 0.215 > 0.05). There were 14 cases (14/51) with positive expression in patients with moderate- and well-differentiated lung carcinoma and 36 cases (36/39) with positive expression in patients with poor-differentiated lung carcinoma, and the difference was statistically significant (χ (2) = 35.068, P = 0.000 < 0.05). There were 37 cases (37/42) with positive expression in patients with lymphatic metastasis and 26 cases (26/48) with positive expression in patients without lymphatic metastasis, and the difference was statistically significant (χ (2) = 12.279, P = 0.000 < 0.05). (2) The mean intratumoral microvessel density (iMVD) was 46.2 ± 6.77 in the field of lung cancer tissue at high magnification under MMP-7-positive condition and 30.8 ± 7.54 in the field of lung cancer tissue at high magnification under MMP-7-negative condition, and the difference was statistically significant (t = 9.641, P = 0.000 < 0.05). (3) The positive rate of bFGF was 12 % in normal tissue section and 63.3 % in non-small cell lung cancer tissue section, and the difference was statistically significant (χ (2) = 34.222, P = 0.000 < 0.05). There were 41 cases (41/56) with positive expression in patients with squamous cell carcinoma and 20 cases (20/34) with positive expression in patients with adenocarcinoma, and the difference was not statistically significant (χ(2) = 2.006, P = 0.157 > 0.05). There were 29 cases (29/51) with positive expression in patients with moderate- and well-differentiated lung carcinoma and 35 cases (35/39) with positive expression in patients with poor-differentiated lung carcinoma, and the difference was statistically significant (χ (2) = 10.085, P = 0.001 < 0.05). There were 37 cases (37/42) with positive expression in patients with lymphatic metastasis and 25 cases (25/48) with positive expression in patients without lymphatic metastasis, and the difference was statistically significant (χ (2) = 13.554, P = 0.001 < 0.05). (4) The (iMVD) was 45.8 ± 7.16 in the field at high magnification under bFGF-positive condition and 31.2 ± 6.46 in the field at high magnification under bFGF-negative condition, and the difference was statistically significant (t = 9.654, P = 0.001 < 0.05). (5) A correlation was demonstrated between MMP-7 and bFGF in non-small cell lung cancer (r = 0.353, P = 0.000 < 0.05). Both MMP-7 and bFGF are participated in the progression of non-small cell lung cancer and exert a synergistic effect during physiological processes including pathogenesis, invasion, and metastasis of non-small cell lung cancer. Therefore, a combined detection of MMP-7 and bFGF for non-small cell lung cancer contributes to predict the progression and prognosis of non-small cell lung cancer, with significant clinical value.
Banday MZ, Sameer AS, Mir AH, et al.Matrix metalloproteinase (MMP) -2, -7 and -9 promoter polymorphisms in colorectal cancer in ethnic Kashmiri population - A case-control study and a mini review.
Gene. 2016; 589(1):81-9 [PubMed
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Matrix metalloproteinases (MMPs) are proteolytic enzymes that play a pivotal role in the transformation and progression of tumors at all stages, especially during the invasion and metastasis. The aim of this study was to determine the genetic association of MMP2, MMP7 and MMP9 promoter polymorphisms with colorectal cancer (CRC) susceptibility and development risk in ethnic Kashmiri population. The genotype frequencies of MMP2-1306C/T, MMP7-181A/G and MMP9-1562C/T SNPs were compared between 142 CRC patients and 184 healthy controls by using PCR-RFLP method. The association between all the three MMP promoter polymorphisms and the modulation of risk of CRC was found to be significant (p≤0.05). The heterozygous genotype (CT) of MMP2-1306C/T SNP and variant genotype (GG) of MMP7-181A/G SNP showed a significant association with decreased risk for the development of CRC [OR, 0.61 (95%CI, 0.37-1.01); p=0.05 and OR, 0.43 (95%CI, 0.20-0.90); p=0.02, respectively] whereas the heterozygous genotype (CT) of MMP9-1562C/T SNP showed a significant association with increased risk for the development of colorectal cancer [OR, 1.88 (95%CI, 1.11-3.18); p=0.02]. Further, the less common MMP9-1562T allele was found to be significantly associated with an increased risk of colorectal cancer [OR, 1.74 (95%CI, 1.15-2.62); p=0.007]. Our results suggest that these MMP2, MMP7 and MMP9 promoter polymorphisms play a role as one of the key modulators of the risk of developing colorectal cancer in Kashmiri population.
Yassin AM, Elnouby M, El-Deeb NM, Hafez EETungsten Oxide Nanoplates; the Novelty in Targeting Metalloproteinase-7 Gene in Both Cervix and Colon Cancer Cells.
Appl Biochem Biotechnol. 2016; 180(4):623-637 [PubMed
] Related Publications
In this study, we synthesized tungsten oxide (WO3) nanoplates, both crystallographic phases and the morphology of the samples were determined by powder x-ray diffraction and the scanning electron microscopy, respectively. The obtained data clarified that, the all prepared WO3·H2O samples were composed of large quantity of nanoplates. The cytotoxicity patterns of nanoplates were checked on both normal and cancer mammalian cell lines. Both nanoplates cytotoxicity did not exceed the 50 % inhibitory concentration (IC50) on the all normal tested cells even by using concentrations up to 1 mg/ml. In addition, orthorhombic tungsten oxide nanoplate was more potent against both Caco2 and Hela cells by showing inhibition percentages in cellular viability 64.749 and 72.27, respectively, and with cancer selectivity index reached 3.2 and 2.6 on both colon and cervix cancer, respectively. The anticancer effects of nanoplates were translated to alteration in both pro-apoptotic and anti-apoptotic genes expressions. Tungsten oxide nanoplates down regulated the expression of B cell lymphoma 2 (Bcl-2) and metalloproteinase-7 (MMP7) genes. In addition, orthorhombic tungsten oxide nanoplates showed more potentiation in IL2 and IL8 induction (40.43 pg/ml) and upregulation of TNF-α gene expression but with lower folds than Escherichia coli lipopolysaccharide (LPS) induction.
Norton N, Advani PP, Serie DJ, et al.Assessment of Tumor Heterogeneity, as Evidenced by Gene Expression Profiles, Pathway Activation, and Gene Copy Number, in Patients with Multifocal Invasive Lobular Breast Tumors.
PLoS One. 2016; 11(4):e0153411 [PubMed
] Free Access to Full Article Related Publications
BACKGROUND: Invasive lobular carcinoma (ILC) comprises approximately ~10-20% of breast cancers. In general, multifocal/multicentric (MF/MC) breast cancer has been associated with an increased rate of regional lymph node metastases. Tumor heterogeneity between foci represents a largely unstudied source of genomic variation in those rare patients with MF/MC ILC.
METHODS: We characterized gene expression and copy number in 2 or more foci from 11 patients with MF/MC ILC (all ER+, HER2-) and adjacent normal tissue. RNA and DNA were extracted from 3x1.5 mm cores from all foci. Gene expression (730 genes) and copy number (80 genes) were measured using Nanostring PanCancer and Cancer CNV panels. Linear mixed models were employed to compare expression in tumor versus normal samples from the same patient, and to assess heterogeneity (variability) in expression among multiple ILC within an individual.
RESULTS: 35 and 34 genes were upregulated (FC>2) and down-regulated (FC<0.5) respectively in ILC tumor relative to adjacent normal tissue, q<0.05. 9/34 down-regulated genes (FIGF, RELN, PROM1, SFRP1, MMP7, NTRK2, LAMB3, SPRY2, KIT) had changes larger than CDH1, a hallmark of ILC. Copy number changes in these patients were relatively few but consistent across foci within each patient. Amplification of three genes (CCND1, FADD, ORAOV1) at 11q13.3 was present in 2/11 patients in both foci. We observed significant evidence of within-patient between-foci variability (heterogeneity) in gene expression for 466 genes (p<0.05 with FDR 8%), including CDH1, FIGF, RELN, SFRP1, MMP7, NTRK2, LAMB3, SPRY2 and KIT.
CONCLUSIONS: There was substantial variation in gene expression between ILC foci within patients, including known markers of ILC, suggesting an additional level of complexity that should be addressed.
Feng L, Xie Y, Zhao Z, Lian WLMX1A inhibits metastasis of gastric cancer cells through negative regulation of β-catenin.
Cell Biol Toxicol. 2016; 32(2):133-9 [PubMed
] Related Publications
Previously, we reported that the LIM homeobox transcription factor 1, alpha (LMX1A) presented tumor-suppressing roles in gastric AGS cells. Here, we showed that LMX1A also inhibits metastasis-related behaviors including migration and invasion of gastric cancer cells. Mechanistic study revealed that the role of LMX1A was mediated by β-catenin, as knockdown of LMX1A upregulated the expression of β-catenin and knockdown of β-catenin reversed the effects of LMX1A silencing. β-catenin is essential for the activation of WNT signaling pathway. Indeed, knockdown of LMX1A activated the expressions of WNT signaling target genes T cell-specific transcription factor 4 (TCF4) and matrix metalloproteinase-7 (MMP7). What is more, the expression of LMX1A was negatively correlated with WNT signaling target genes in two datasets of human gastric cancer tissues. Thus, our study revealed an anti-metastatic role of LMX1A in gastric cancer which is mediated by the negative regulation of β-catenin signaling target genes.
Lv YF, Dai H, Yan GN, et al.Downregulation of tumor suppressing STF cDNA 3 promotes epithelial-mesenchymal transition and tumor metastasis of osteosarcoma by the Wnt/GSK-3β/β-catenin/Snail signaling pathway.
Cancer Lett. 2016; 373(2):164-73 [PubMed
] Related Publications
Epithelial to mesenchymal transition (EMT) has received considerable attention as a conceptual paradigm for explaining the invasive and metastatic behavior of cells during cancer progression. Our previous study showed that loss of expression of TSSC3 is positively associated with osteosarcoma malignancy and progression. However, whether TSSC3 mediates EMT in osteosarcoma is poorly understood. In the present study, we determined that TSSC3 downregulation induced cell migration and invasion ability and promoted mesenchymal transition of osteosarcoma cells by upregulating mesenchymal markers and inhibiting the epithelial markers. Furthermore, TSSC3 downregulation elicited a signaling cascade that included increased levels of Wnt3a and LRP5, inactivation of GSK-3β, accumulation of nuclear β-catenin and Snail, the augmented binding of β-catenin to TCF-4, and accordingly increased the expression of Wnt target genes (CD44, MMP7). The gene knockdown of these signaling proteins could inhibit TSSC3 downregulation-promoted EMT, migration, and invasion in osteosarcoma. Finally, TSSC3 overexpression obviously inhibited cell migration, invasion, and repressed mesenchymal phenotypes, reducing lung metastasis through GSK-3β activation. Collectively, TSSC3 downregulation promotes the EMT of osteosarcoma cells by regulating EMT markers via a signal transduction pathway that involves Snail, Wnt-β-catenin/TCF, and GSK-3β.
Hsa-miRNA-326 (miR-326) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-326 on non-small cell lung cancer (NSCLC) is still ambiguous. In this study, we investigated the role of miR-326 on the development of NSCLC. The results indicated that miR-326 was significantly down-regulated in primary tumor tissues and very low levels were found in NSCLC cell lines. Ectopic expression of miR-326 in NSCLC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4 and up-regulation of p57(Kip2) and p21(Waf1/Cip1). In addition, miR-326 induced apoptosis, as indicated by concomitantly with up-regulation of key apoptosis protein cleaved caspase-3, and down-regulation of anti-apoptosis protein Bcl2. Moreover, miR-326 inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene CCND1 was revealed to be a putative target of miR-326, which was inversely correlated with miR-326 expression in NSCLC. Taken together, our results demonstrated that miR-326 played a pivotal role on NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic CCND1.
Xu CL, Wang JZ, Xia XP, et al.Rab11-FIP2 promotes colorectal cancer migration and invasion by regulating PI3K/AKT/MMP7 signaling pathway.
Biochem Biophys Res Commun. 2016; 470(2):397-404 [PubMed
] Related Publications
Rab11-family interacting proteins (Rab11-FIPs) belong to an evolutionarily conserved protein family and act as effector molecules for the Rab11 family of small GTPases. Recent evidence suggests that Rab11-FIPs have important roles in tumor progression and metastasis. However, the contribution of Rab11-FIPs to colorectal carcinoma (CRC) remains elusive. Our study focuses on elucidating the role of Rab11-FIP2 in the migration and invasion of colorectal cancer cells. We firstly found upregulation of Rab11-FIP2 in CRC tissues compared with peritumor tissues by oncomine data-mining analysis, western blot analysis and immunohistochemistry (IHC) analysis, respectively. Then, we demonstrated that knockdown of Rab11-FIP2 via siRNAs transfection resulted in a decrease in migration and invasion of CRC cells, while overexpression of Rab11-FIP2 via lentiviral infection increased migration and invasion of CRC cells. In addition, we verified that Rab11-FIP2 promoted migration and invasion of CRC cells through upregulating MMP7 expression. Finally, using several kinase inhibitors, our results showed that Rab11-FIP2 regulated MMP7 expression through activating PI3K/Akt signaling. Our data suggested a potential role of Rab11-FIP2 in tumor progression and provided novel insights into the mechanism of how Rab11-FIP2 positively regulated cell migration and invasion in CRC cells.
BACKGROUND: Grb2-associated binder 2 (Gab2), a scaffolding adaptor protein, has recently been implicated in cancer progression. However, the role of Gab2 in the progression and metastasis of colorectal cancer (CRC) remains unclear.
METHODS: Gab2 expression was assessed in CRC patient specimens as well as in CRC cell lines. Recombinant lentivirus vector containing Gab2 gene and its small interfering RNAs were constructed and introduced into CRC cells. Cell migration and invasion ability were evaluated by transwell assays in vitro, and in vivo metastasis was performed on nude mice model. Moreover, the expression of Gab2 and epithelial-to-mesenchymal transition (EMT)-associated proteins (E-cadherin and vimentin) were assessed by western blot and qRT-PCR in CRC cells to evaluate the correlation between Gab2 and EMT. Finally, we evaluated the impact of Gab2 on the activation of its downstream signaling effectors, and furthermore the effects of these pathways on Gab2 induced-EMT were also detected.
RESULTS: We confirmed that increased Gab2 expression correlated with higher tumor node metastasis stage and highly invasive CRC cell lines. Ectopic expression of Gab2 promoted metastasis of CRC cells, whereas silencing of Gab2 resulted in inhibited metastasis both in vitro and in vivo. Overexpression of Gab2 in CRC cells induced EMT, whereas knockdown of Gab2 had the opposite effect. Furthermore, upregulation of Gab2 expression obviously stimulated the activation of extracellular signal-regulated kinase-1/2 (ERK1/2), and increased the expression of matrix metalloproteinase-7 (MMP7) and matrix metalloproteinase-9 (MMP9) in CRC cells. Conversely, downregulation of Gab2 expression significantly decreased the activation of ERK1/2, and inhibited MMP7 and MMP9 expression. U0126, an inhibitor of mitogen-activated protein kinase (MEK), can reverse the effects of Gab2 on EMT.
CONCLUSIONS: Our work highlights that Gab2 induces EMT through the MEK/ERK/MMP pathway, which in turn promotes intestinal tumor metastasis.
Wang WG, Chen SJ, He JS, et al.The tumor suppressive role of RASSF1A in osteosarcoma through the Wnt signaling pathway.
Tumour Biol. 2016; 37(7):8869-77 [PubMed
] Related Publications
Ras-association domain family 1 isoform A (RASSF1A) is a tumor suppressor gene and its expression is lost in numerous types of cancer cells, including primary osteosarcoma cells. However, its functional significance in osteosarcoma has not been well defined. The messenger RNA (mRNA) expression of RASSF1A in osteosarcoma tissues and corresponding non-tumoral tissues was measured by real-time PCR. Overexpression of RASSF1A was established by an adenoviral vector expressing RASSF1A. Cell migration and invasion were analyzed in transwells. Apoptosis and cell cycle were analyzed using flow cytometry. Wnt/β-catenin activity was measured by TCF reporter dual-luciferase assay. Cell viability was measured by MTT assay. Protein expression was detected by Western blot. RASSF1A mRNA expression was significantly lower in osteosarcoma tissues than that in the corresponding non-tumoral tissues. The lowered RASSF1A expression correlated with the clinical severity of osteosarcoma. rAd-RASSF1A injection significantly inhibited the growth of xenograft MNNG/HOS tumors in mice. Overexpression of RASSF1A resulted in significant inhibition of the proliferation, migration, and invasion; induced apoptosis; and arrested cell cycle at G0/G1 phase in both the MNNG/HOS and SaOS2 cells. Overexpression of RASSF1A inhibited the Wnt/β-catenin activity, decreased phosphorylation of Akt/glycogen synthase kinase-3-β (GSK3-β), and increased phosphorylation of mammalian sterile 20-like kinase 1 (MST1). Overexpression of RASSF1A downregulated the cyclin D1, c-Myc, and matrix metalloproteinase-7 (MMP-7) protein levels. RASSF1A functions as a tumor suppressor in osteosarcoma and exerts anti-cancer roles through regulating Akt/GSK-3-Wnt/β-catenin signaling.
Entire or partial deletions of the male-specific Y chromosome are associated with tumorigenesis, but whether any male-specific genes located on this chromosome play a tumor-suppressive role is unknown. Here, we report that the histone H3 lysine 4 (H3K4) demethylase JARID1D (also called KDM5D and SMCY), a male-specific protein, represses gene expression programs associated with cell invasiveness and suppresses the invasion of prostate cancer cells in vitro and in vivo. We found that JARID1D specifically repressed the invasion-associated genes MMP1, MMP2, MMP3, MMP7, and Slug by demethylating trimethyl H3K4, a gene-activating mark, at their promoters. Our additional results demonstrated that JARID1D levels were highly downregulated in metastatic prostate tumors compared with normal prostate tissues and primary prostate tumors. Furthermore, the JARID1D gene was frequently deleted in metastatic prostate tumors, and low JARID1D levels were associated with poor prognosis in prostate cancer patients. Taken together, these findings provide the first evidence that an epigenetic modifier expressed on the Y chromosome functions as an anti-invasion factor to suppress the progression of prostate cancer. Our results also highlight a preclinical rationale for using JARID1D as a prognostic marker in advanced prostate cancer.
Voltage-gated Na+ channels (VGSCs) are membrane proteins which are normally expressed in excitable cells but have also been detected in cancer cells, where they are thought to be involved in malignancy progression. In this study we examined the ion current and expression profile of VGSC (Nav1.5) in estrogen receptor (ER)-positive (MCF-7) and silenced (pII) breast cancer cells and its possible influence on their proliferation, motility and invasion. VGSC currents were analysed by whole cell patch clamp recording. Nav1.5 expression and localization, in response to EGF stimulation, was examined by western blotting and immunofluorescence respectively. Cell invasion (under-agarose and Matrigel assays), motility (wound healing assay) and proliferation (MTT assay) were assessed in pII cells in response to VGSC blockers, phenytoin (PHT) and tetrodotoxin (TTX), or by siRNA knockdown of Nav1.5. The effect of PHT and TTX on modulating EGF-induced phosphorylation of Akt and ERK1/2 was determined by western blotting. Total matrix metalloproteinase (MMP) was determined using a fluorometric-based activity assay. The level of various human proteases was detected by using proteome profiler array kit. VGSC currents were detected in pII cells, but were absent in MCF-7. Nav1.5 showed cytoplasmic and perinuclear expression in both MCF-7 and pII cells, with enhanced expression upon EGF stimulation. Treatment of pII cells with PHT, TTX or siRNA significantly reduced invasion towards serum components and EGF, in part through reduction of P-ERK1/2 and proteases such as cathepsin E, kallikrein-10 and MMP-7, as well as total MMP activity. At high concentrations, PHT inhibited motility while TTX reduced cell proliferation. Pharmacological or genetic blockade of Nav1.5 may serve as a potential anti-metastatic therapy for breast cancer.
Jiang Q, He M, Ma MT, et al.MicroRNA-148a inhibits breast cancer migration and invasion by directly targeting WNT-1.
Oncol Rep. 2016; 35(3):1425-32 [PubMed
] Related Publications
Wnt/β-catenin signaling pathway influences embryonic development, cell polarity and adhesion, apoptosis and tumorigenesis. MicroRNAs (miRNAs) function as important regulators of the tumorigenesis and metastasis. In the present study, we aimed to find novel targets and mechanisms of microRNA-148a (miR-148a) in regulating the migration and invasion of breast cancer cells. In the present study, miR-148a was found downregulated in human breast cancer tissues and cell lines. The ectopic miR-148a expression inhibited the migration and invasion of MCF-7 and MDA-MB-231 breast cancer cells. Furthermore, we demonstrated that WNT-1, one of the ligands of Wnt/β-catenin signaling pathway, was a direct target of miR-148a. The overexpression of miR-148a reduced the mRNA and protein expression levels of WNT-1, also decreased the expression levels of the key components of Wnt/β-catenin pathway, including β-catenin, metalloproteinase-7 (MMP-7) and T-cell factor-4 (TCF-4) in MCF-7 and MDA-MB-231 cells. In addition, the data showed that the expression of WNT-1 was significantly higher in human breast cancer tissues compared with the adjacent normal tissues and the expression of miR-148a was negatively correlated with the WNT-1 expression in human breast cancer tissues. Taken together, our results suggest that miR-148a can suppress the migration and invasion of breast cancer cells by targeting WNT-1 and inhibiting Wnt/β-catenin signaling pathway and this will provide new insights into the molecular mechanisms of breast cancer metastasis.
SET7/9, a histone methyltransferase, has two distinct functions for lysine methylation. SET7/9 methylates non-histone proteins, such as p53, and participates in their posttranslational modifications. Although SET7/9 transcriptionally activate the genes via H3K4 mono-methylation, its target genes are poorly understood. To clarify whether or not SET7/9 is related to carcinogenesis, we studied alterations of SET7/9 in gastric cancers (GCs). Among the 376 primary GCs, 129 cases (34.3%) showed loss or weak expression of SET7/9 protein compared to matched non-cancerous tissues by immunohistochemistry. Reduced SET7/9 expression was significantly correlated with clinical aggressiveness and worse prognosis. Knockdown of SET7/9 in GC cells markedly increased cell proliferation, migration and invasion. Expression of SREK1IP1, PGC and CCDC28B were inhibited in GC cells with SET7/9 knockdown, while matrix metalloproteinase genes (MMP1, MMP7 and MMP9) were activated. SET7/9 bound and mono-methylated H3K4 at the region of the approximately 4-6 kb upstream from the SREK1IP1 transcriptional start site and the promoters of PGC and CDC28B. Cell proliferation, migration and invasion, and expression of three MMPs were increased in GC cells with SREK1IP knockdown, which were similar to those of SET7/9 knockdown. These data suggest that SET7/9 has tumor suppressor functions, and loss of SET7/9 may contribute to gastric cancer progression.
Geng D, Zhao W, Feng Y, Liu JOverexpression of Rab25 promotes hepatocellular carcinoma cell proliferation and invasion.
Tumour Biol. 2016; 37(6):7713-8 [PubMed
] Related Publications
Rab25 was reported to be associated with several human cancers and malignant biological behavior of cancer cells. The goal of the present study was to determine its expression pattern and biological function in human hepatocellular carcinoma (HCC). We examined Rab25 protein in 92 cases of HCC tissues and 3 HCC cell lines. The results showed that Rab25 was upregulated in HCC tissues and cells compared with normal liver tissues and cell line. Rab25 overexpression correlated with advanced tumor stage and nodal metastasis. Rab25 small interfering RNA (siRNA) was employed in Bel7402 and SK-Hep-1 cell lines. Cell Counting Kit-8 (CCK-8) assay and colony formation assay showed that Rab25 depletion blocked cell growth rate and inhibited colony formation ability. Transwell assay showed that Rab25 depletion negatively regulated the invading ability of HCC cells. To explore the possible mechanisms, we checked several signaling pathways and found that Rab25 depletion downregulated AKT phosphorylation. In addition, luciferase reporter assay showed that Rab25 depletion inhibited the Wnt signaling pathway and its target genes such as cyclin D1, c-myc, and MMP7. In conclusion, Rab25 is overexpressed in human HCC and contributes to cancer cell proliferation and invasion possibly through regulation of the Wnt signaling pathway.
BACKGROUND: Regulation of MMP expression by activation of mTOR signalling has been demonstrated for several tumor types, but has thus far not been confirmed in gastric cancer.
FINDINGS: The study compromised 128 patients who underwent gastric resection for cancer (66.4 % male; 86 intestinal, 42 diffuse type). Immunohistochemical staining of MMPs was performed to analyse the topographical pattern of MMP expression at the tumor center and the invasive front, respectively. MMP2 showed higher expression at the invasive front compared to the tumor center, whereas MMP7 staining scores were higher in the tumor center, and there was no difference for MMP9. The expression of p-mTOR was higher in the tumor center than at the invasive front, with a similar trend for mTOR. For intestinal type gastric cancer there was a weak correlation of MMP9 with expression of mTOR in the tumor center. Otherwise, there was no correlation of the MMPs with mTOR. By treatment of MKN45 gastric cancer cells with rapamycin, a reduction of p-mTOR in the Western blot was achieved; however, expression of MMPs remained unaffected.
CONCLUSIONS: Expression of MMP2 and MMP7 in gastric cancer is not associated with mTOR, MMP9 expression might be related to mTOR signalling in a subset of tumors.
Su CCTanshinone IIA decreases the migratory ability of AGS cells by decreasing the protein expression of matrix metalloproteinases, nuclear factor κB-p65 and cyclooxygenase-2.
Mol Med Rep. 2016; 13(2):1263-8 [PubMed
] Related Publications
During progression of gastric cancer, degradation of the extracellular matrix by matrix metalloproteinases (MMPs) has been associated with poor prognosis. Tanshinone IIA (Tan-IIA) exerts antitumor activity in a variety of human cancer cells. It is extracted from Danshen (Salviae miltiorrhizae radix), and induces apoptosis and inhibits the proliferation of gastric cancer cells. However, the molecular mechanisms underlying the inhibition of migration in gastric cancer by Tan-IIA have not been fully elucidated. In the present study, AGS cell migration ability was evaluated using a wound-healing assay. The protein expression levels of nuclear factor (NF)-κB-p65, cyclooxygenase (COX)-2, MMP-2, -7, and -9 and β-actin in AGS cells were measured by western blotting. The results demonstrated that AGS cells treated with Tan-IIA exhibit decreased protein expression levels of NF-κB-p65, COX-2, and MMP-2, -7 and -9. The results also indicate that Tan-IIA inhibits migration ability in a dose- and time-dependent manner. These findings demonstrate that Tan-IIA inhibits the migration ability of AGS human gastric cancer cells and that decreasing the protein expression of NF-κB-p65, COX-2, and MMP-2, -7 and -9 may be an underlying molecular mechanism.
Kobayashi T, Masaki T, Nozaki E, et al.Microarray Analysis of Gene Expression at the Tumor Front of Colon Cancer.
Anticancer Res. 2015; 35(12):6577-81 [PubMed
] Related Publications
Budding or the presence poorly differentiated clusters at the boundary of cancer tissue is a pathologically important finding and serves as a prognostic factor in colorectal cancer. However, few studies have examined the cancer tissue boundary in clinical samples. The purpose of the present study was to examine gene expression at the tumor front of colon cancer in surgically resected samples. Cancer tissues were obtained by laser microdissection of 20 surgically resected specimens. Genes with significantly different microarray signals between the tumor front and the tumor center were identified. Among genes showing significant up-regulation at the tumor front were six chemokines [chemokine c-c motif ligand (CCL)2 and -18, chemokine (C-X-C motif) ligand (CXCL)9-11, and interleukin 8 (IL8)], and two apoptosis-related molecules [ubiquitin D (UBD) and baculoviral iap repeat-containing 3 (BIRC3)]. Expression of laminin gamma 2 (LAMC2), matrix metallopeptidase 7 (MMP7) and epithelial-mesenchymal transition (EMT)-related molecules were elevated in the tumor front, but their fold changes were smaller than those of the aforementioned genes. These results suggest that chemokines, in addition to EMT-related molecules, may play important roles in invasion of colon cancer.
Banerjee K, Resat HConstitutive activation of STAT3 in breast cancer cells: A review.
Int J Cancer. 2016; 138(11):2570-8 [PubMed
] Article available free on PMC
after 01/06/2017 Related Publications
Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in numerous cancer types, including more than 40% of breast cancers. In contrast to tight regulation of STAT3 as a latent transcription factor in normal cells, its signaling in breast cancer oncogenesis is multifaceted. Signaling through the IL-6/JAK/STAT3 pathway initiated by the binding of IL-6 family of cytokines (i.e., IL-6 and IL-11) to their receptors have been implicated in breast cancer development. Receptors with intrinsic kinase activity such as EGFR and VEGFR directly or indirectly induce STAT3 activation in various breast cancer types. Aberrant STAT3 signaling promotes breast tumor progression through deregulation of the expression of downstream target genes which control proliferation (Bcl-2, Bcl-xL, Survivin, Cyclin D1, c-Myc and Mcl-1), angiogenesis (Hif1α and VEGF) and epithelial-mesenchymal transition (Vimentin, TWIST, MMP-9 and MMP-7). These multiple modes of STAT3 regulation therefore make it a central linking point for a multitude of signaling processes. Extensive efforts to target STAT3 activation in breast cancer had no remarkable success in the past because the highly interconnected nature of STAT3 signaling introduces lack of selectivity in pathway identification for STAT3 targeted molecular therapies or because its role in tumorigenesis may not be as critical as it was thought. This review provides a full spectrum of STAT3's involvement in breast cancer by consolidating the knowledge about its role in breast cancer development at multiple levels: its differential regulation by different receptor signaling pathways, its downstream target genes, and modification of its transcriptional activity by its coregulatory transcription factors.
Wu DIsocitrate dehydrogenase 2 inhibits gastric cancer cell invasion via matrix metalloproteinase 7.
Tumour Biol. 2016; 37(4):5225-30 [PubMed
] Related Publications
Isocitrate dehydrogenase 2 (IDH2) is a mitochondrial NADP-dependent isocitrate dehydrogenase and has been found to be a tumor suppressor in several types of tumors. However, the roles of IDH2 in hepatocellular carcinoma (GC) as well as underlying mechanisms remain unknown. Here, the IDH2 and matrix metalloproteinase 7 (MMP7) levels in the specimens from 30 GC patients were investigated by Western blot and ELISA, respectively. Their relationship was examined by correlation analyses. Patient survival with high IDH2 levels and low IDH2 levels was compared. IDH2 levels, and MMP7 levels were modified in a human GC cell line. The effects of IDH2 or MMP7 modulation on the expression of each other were analyzed. The dependence of nuclear factor κB (NF-κB) signaling was examined using a specific inhibitor. We found that the IDH2 levels significantly decreased in GC, and were even lower in GC with metastases, compared to those without metastases. IDH2 levels inversely correlated with MMP7 levels in GC. GC patients with low IDH2 had lower 5-year survival. MMP7 levels did not regulate IDH2 levels, while IDH2 inhibited MMP7 levels in GC cells, in a NF-κB signaling dependent manner. Together, these data suggest that IDH2 may be a tumor suppressor in that its loss may promote malignant progression of GC via NF-κB-dependent increases in MMP7 activity.
Jiang Q, He M, Guan S, et al.MicroRNA-100 suppresses the migration and invasion of breast cancer cells by targeting FZD-8 and inhibiting Wnt/β-catenin signaling pathway.
Tumour Biol. 2016; 37(4):5001-11 [PubMed
] Related Publications
Wnt/β-catenin signaling pathway plays a major role in the cancer metastasis. Several microRNAs (miRNAs) are contributed to the inhibition of breast cancer metastasis. Here, we attempted to find novel targets and mechanisms of microRNA-100 (miR-100) in regulating the migration and invasion of breast cancer cells. In this study, we found that miR-100 expression was downregulated in human breast cancer tissues and cell lines. The overexpression of miR-100 inhibited the migration and invasion of MDA-MB-231 breast cancer cells. Inversely, the downregulation of miR-100 increased the migration and invasion of MCF-7 breast cancer cells. Furthermore, FZD-8, a receptor of Wnt/β-catenin signaling pathway, was demonstrated a direct target of miR-100. The overexpression of miR-100 decreased the expression levels not only FZD-8 but also the key components of Wnt/β-catenin pathway, including β-catenin, metalloproteniase-7 (MMP-7), T-cell factor-4 (TCF-4), and lymphoid enhancing factor-1 (LEF-1), and increased the protein expression levels of GSK-3β and p-GSK-3β in MDA-MB-231 cells, and the transfection of miR-100 inhibitor in MCF-7 cells showed the opposite effects. In addition, the expression of miR-100 was negatively correlated with the FZD-8 expression in human breast cancer tissues. Overall, these findings suggest that miR-100 suppresses the migration and invasion of breast cancer cells by targeting FZD-8 and inhibiting Wnt/β-catenin signaling pathway and manipulation of miR-100 may provide a promoting therapeutic strategy for cancer breast treatment.
Xie B, Zhang Z, Wang H, et al.Genetic polymorphisms in MMP 2, 3, 7, and 9 genes and the susceptibility and clinical outcome of cervical cancer in a Chinese Han population.
Tumour Biol. 2016; 37(4):4883-8 [PubMed
] Related Publications
Matrix metalloproteases (MMPs) are proteolytic enzymes that contribute to all stages of tumor progression, including the invasion and metastasis. However, there are no data about the role of MMP polymorphism in the development of cervical cancer. A hospital-based case-control study was conducted in 230 patients with cervical cancer and 230 healthy controls to investigate the possible association between the MMP2 rs243865, MMP3 rs3025058, MMP7 rs11568818, and MMP9 rs3918242 polymorphisms, respectively, and the risk of cervical cancer. Our results suggested that the MMP2 rs243865-1306 C/T was significantly associated with an increased risk of cervical cancer (CT vs. CC, OR = 1.46; 95 % CI 1.18-3.55; P = 0.032; TT vs. CC, OR = 1.72; 95 % CI 1.28-4.02; P = 0.031; CT + TT vs. CC, OR = 1.43; 95 % CI 1.21-3.44; P = 0.029). Similarly, the MMP7 rs11568818-181A/G genotypes can also elevate the risk of cervical cancer in all genetic models. However, the genotype and allele frequencies of MMP3 rs3025058 and MMP9 rs3918242 polymorphisms in cervical cancer patients were not significantly different from controls. Further analysis showed MMP2 rs243865 and MMP7 rs11568818 genotypes were associated with advanced tumor stages of cervical cancer patients. More interestingly, the MMP2 rs243865 and MMP7 rs11568818 genotype was statistically significantly associated with a poor survival in cervical cancer patients. Our results showed that the MMP2 rs243865 and MMP7 rs11568818 genotypes e were associated with increased susceptibility and development of cervical cancer in Chinese Han population.
Sun C, Sang M, Li S, et al.Hsa-miR-139-5p inhibits proliferation and causes apoptosis associated with down-regulation of c-Met.
Oncotarget. 2015; 6(37):39756-92 [PubMed
] Article available free on PMC
after 01/06/2017 Related Publications
Hsa-miRNA-139-5p (miR-139-5p) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-139-5p on lung cancer is still ambiguous. In this study, we investigated the role of miR-139-5p on development of lung cancer. Results indicated miR-139-5p was significantly down-regulated in primary tumor tissues and very low levels were found in a non-small cell lung cancer (NSCLC) cell lines. Ectopic expression of miR-139-5p in NSCLC cell lines significantly suppressed cell growth through inhibition of cyclin D1 and up-regulation of p57(Kip2). In addition, miR-139-5p induced apoptosis, as indicated by up-regulation of key apoptosis gene cleaved caspase-3, and down-regulation of anti-apoptosis gene Bcl2. Moreover, miR-139-5p inhibited cellular metastasis through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene c-Met was revealed to be a putative target of miR-139-5p, which was inversely correlated with miR-139-5p expression. Taken together, our results demonstrated that miR-139-5p plays a pivotal role in lung cancer through inhibiting cell proliferation, metastasis, and promoting apoptosis by targeting oncogenic c-Met.