title: Hsa-miR-134 suppresses non-small cell lung cancer (NSCLC) development through down-regulation of CCND1.
abstract: Hsa-miRNA-134 (miR-134) has recently been discovered to have anticancer efficacy in different organs. However, the role of miR-134 on non-small cell lung cancer (NSCLC) is still ambiguous. In this study, we investigated the role of miR-134 on the development of NSCLC. The results indicated that miR-134 was significantly down-regulated in primary tumor tissues and very low levels were found in NSCLC cell lines. Ectopic expression of miR-134 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-134 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-134 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-134, which was inversely correlated with miR-134 expression in NSCLC. Taken together, our results demonstrated that miR-134 played a pivotal role on NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic CCND1.
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan, P. R. China.
authors.forename: Cheng-Cao
authors.initials: CC
authors.lastname: Sun
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan, P. R. China.|Wuhan Hospital for The Prevention and Treatment of Occupational Diseases, Wuhan, P. R. China.
authors.forename: Shu-Jun
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan, P. R. China.
authors.forename: De-Jia
authors.initials: DJ
authors.lastname: Li
mesh_terms: D000072283:A549 Cells; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D014183:Transplantation, Heterologous
chemical_list: C530104:CCND1 protein, human; C569273:MIRN134 microRNA, human; D035683:MicroRNAs; D019938:Cyclin D1
keywords: apoptosis; cyclin D1; hsa-miRNA-134 (miR-134); non-small cell lung cancer (NSCLC); proliferation