title: Hsa-miR-329 exerts tumor suppressor function through down-regulation of MET in non-small cell lung cancer.
abstract: MicroRNAs (miRNAs) act as key regulators of multiple cancers. Hsa-miR-329 (miR-329) functions as a tumor suppressor in some malignancies. However, its role on lung cancer remains poorly understood. In this study, we investigated the role of miR-329 on the development of lung cancer. The results indicated that miR-329 was decreased in primary lung cancer tissues compared with matched adjacent normal lung tissues and very low levels were found in a non-small cell lung cancer (NSCLC) cell lines. Ectopic expression of miR-329 in lung cancer cell lines substantially repressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibiting cyclin D1, cyclin D2 and up-regulatiing p57(Kip2) and p21(WAF1/CIP1). In addition, miR-329 promoted NSCLC cell apoptosis, as indicated by up-regulation of key apoptosis gene cleaved caspase-3, and down-regulation of anti-apoptosis gene Bcl2. Moreover, miR-329 inhibited cellular migration and invasiveness through inhibiting matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene MET was revealed to be a putative target of miR-329, which was inversely correlated with miR-329 expression. Furthermore, down-regulation of MET by siRNA performed similar effects to over-expression of miR-329. Collectively, our results demonstrated that miR-329 played a pivotal role in lung cancer through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic MET.
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: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan, P. R. China.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Pan
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan, P. R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan, P. R. China.
authors.forename: Cui-Li
authors.initials: CL
authors.lastname: Yang
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan, P. R. China.
authors.forename: Yong-Yong
authors.initials: YY
authors.lastname: Xi
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan, P. R. China.
authors.forename: De Jia
authors.initials: de J
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; 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; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; 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; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D014183:Transplantation, Heterologous
chemical_list: D020413:3' Untranslated Regions; C584396:MIRN329 microRNA, human; D035683:MicroRNAs; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: MET; apoptosis; hsa-miRNA-329(miR-329); non-small cell lung cancer (NSCLC); proliferation