title: MicroRNA-34a inhibits the proliferation and promotes the apoptosis of non-small cell lung cancer H1299 cell line by targeting TGFβR2.
abstract: MicroRNAs (MiRNAs) are small non-coding RNA molecules which act as important regulators of post-transcriptional gene expression by binding 3'-untranslated region (3'-UTR) of target messenger RNA (mRNA). In this study, we analyzed miRNA-34a (miR-34a) as a tumor suppressor in non-small cell lung cancer (NSCLC) H1299 cell line. The expression level of miR-34a in four different NSCLC cell lines, H1299, A549, SPCA-1, and HCC827, was significantly lower than that in the non-tumorigenic bronchial epithelium cell line BEAS-2B. In human NSCLC tissues, miR-34a expression level was also significantly decreased in pT2-4 compared with the pT1 group. Moreover, miR-34a mimic could inhibit the proliferation and triggered apoptosis in H1299 cells. Luciferase assays revealed that miR-34a inhibited TGFβR2 expression by targeting one binding site in the 3'-UTR of TGFβR2 mRNA. Quantitative real-time PCR (qRT-PCR) and Western blot assays verified that miR-34a reduced TGFβR2 expression at both mRNA and protein levels. Furthermore, downregulation of TGFβR2 by siRNA showed the same effects on the proliferation and apoptosis as miR-34a mimic in H1299 cells. Our results demonstrated that miR-34a could inhibit the proliferation and promote the apoptosis of H1299 cells partially through the downregulation of its target gene TGFβR2.
authors.affiliation: School of Life Sciences, Shanghai University, Shanghai, 200444, China.
authors.forename: Zhong-Liang
authors.initials: ZL
authors.lastname: Ma
authors.forename: Pin-Pin
authors.initials: PP
authors.lastname: Hou
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Li
authors.forename: De-Tao
authors.initials: DT
authors.lastname: Wang
authors.forename: Tian-Wei
authors.initials: TW
authors.lastname: Yuan
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: Wei
authors.forename: Bo-Tao
authors.initials: BT
authors.lastname: Zhao
authors.forename: Jia-Tao
authors.initials: JT
authors.lastname: Lou
authors.forename: Xin-Tai
authors.initials: XT
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.forename: You-Xin
authors.initials: YX
authors.lastname: Jin
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II