title: MiR-142-3p represses TGF-β-induced growth inhibition through repression of TGFβR1 in non-small cell lung cancer.
abstract: TGFβR1 plays an important role in TGF-β signaling transduction and serves as a tumor suppressor. Our previous studies show that reduced expression of TGFβR1 is common in non-small cell lung cancer (NSCLC) and TGFβR1 variants confer risk of NSCLC. However, the epigenetic mechanisms underlying the role of TGFβR1 in NSCLC carcinogenesis are still elusive. We investigated the function and regulation of TGF-β signaling-based miRNAs in NSCLC. Computational algorithms predicted that the 3'-untranslated region (3'-UTR) of TGFβR1 is a target of miR-142-3p. Here a luciferase reporter assay confirmed that miR-142-3p can directly bind to 3'-UTR of TGFβR1. Overexpression of miR-142-3p in NSCLC A549 cells suppressed expression of TGFβR1 mRNA and protein, while knockdown of endogenous miR-142-3p led to increased expression of TGFβR1. On TGF-β1 stimulation, stable overexpression of miR-142-3p attenuated phosphorylation of SMAD3, an indispensable downstream effector in canonical TGF-β/Smad signaling, via repression of TGFβR1 in A549 cells. Furthermore, miR-142-3p-mediated down-regulation of TGFβR1 weakened TGF-β-induced growth inhibition effect, and this effect was reversed by stable knockdown of endogenous miR-142-3p in A549 cells. In NSCLC tissues, miR-142-3p expression was increased and inversely correlated with TGFβR1 expression. These data demonstrate that miR-142-3p influences the proliferation of NSCLC cells through repression of TGFβR1.
authors.affiliation: Soochow University Laboratory of Cancer Molecular Genetics and Suzhou Key Laboratory for Molecular Cancer Genetics, Suzhou, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Lei
authors.affiliation: Soochow University Laboratory of Cancer Molecular Genetics and Suzhou Key Laboratory for Molecular Cancer Genetics, Suzhou, China.
authors.forename: Guili
authors.initials: G
authors.lastname: Xu
authors.affiliation: Soochow University Laboratory of Cancer Molecular Genetics and Suzhou Key Laboratory for Molecular Cancer Genetics, Suzhou, China.
authors.forename: Longqiang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Soochow University Laboratory of Cancer Molecular Genetics and Suzhou Key Laboratory for Molecular Cancer Genetics, Suzhou, China.
authors.forename: Haiping
authors.initials: H
authors.lastname: Yang
authors.affiliation: Soochow University Laboratory of Cancer Molecular Genetics and Suzhou Key Laboratory for Molecular Cancer Genetics, Suzhou, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Suzhou Key Laboratory for Molecular Cancer Genetics, Suzhou, China First Affiliated Hospital, Medical College of Soochow University, Suzhou, China; and.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Soochow University Laboratory of Cancer Molecular Genetics and Suzhou Key Laboratory for Molecular Cancer Genetics, Suzhou, China htzhang@suda.edu.cn.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D039621:Eukaryotic Initiation Factor-3 / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D035683:MicroRNAs / Q000096:biosynthesis / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D039621:Eukaryotic Initiation Factor-3; C555159:MIRN142 microRNA, human; D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; C096013:EIF3I protein, human
keywords: NSCLC; cell proliferation; epigenetic mechanism; miRNAs; p-SMAD3