title: Smad3-related miRNAs regulated oncogenic TRIB2 promoter activity to effectively suppress lung adenocarcinoma growth.
abstract: MicroRNAs (miRNAs) and Smad3, as key transcription factors in transforming growth factor-β1 (TGF-β1) signaling, help regulate various physiological and pathological processes. We investigated the roles of Smad3-regulated miRNAs with respect to lung adenocarcinoma cell apoptosis, proliferation, and metastasis. We observed that Smad3 and phospho-SMAD3 (p-Smad3) were decreased in miR-206- (or miR-140)-treated cells and there might be a feedback loop between miR-206 (or miR-140) and TGF-β1 expression. Smad3-related miRNAs affected tribbles homolog 2 (TRIB2) expression by regulating trib2 promoter activity through the CAGACA box. MiR-206 and miR-140 inhibited lung adenocarcinoma cell proliferation in vitro and in vivo by suppressing p-Smad3/Smad3 and TRIB2. Moreover, lung adenocarcinoma data supported a suppressive role for miR-206/miR-140 and an oncogenic role for TRIB2-patients with higher TRIB2 levels had poorer survival. In summary, miR-206 and miR-140, as tumor suppressors, induced lung adenocarcinoma cell death and inhibited cell proliferation by modifying oncogenic TRIB2 promoter activity through p-Smad3. MiR-206 and miR-140 also suppressed lung adenocarcinoma cell metastasis in vitro and in vivo by regulating EMT-related factors.
authors.affiliation: Key Laboratory of Tumor Molecular Biology in Binzhou Medical University, Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, ShanDong, P.R.China.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Tumor Molecular Biology in Binzhou Medical University, Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, ShanDong, P.R.China.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Yan
authors.affiliation: Key Laboratory of Tumor Molecular Biology in Binzhou Medical University, Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, ShanDong, P.R.China.
authors.forename: Yue-Mei
authors.initials: YM
authors.lastname: Liu
authors.affiliation: Key Laboratory of Tumor Molecular Biology in Binzhou Medical University, Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, ShanDong, P.R.China.
authors.forename: You-Jie
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Key Laboratory of Tumor Molecular Biology in Binzhou Medical University, Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, ShanDong, P.R.China.
authors.forename: Han-Han
authors.initials: HH
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Tumor Molecular Biology in Binzhou Medical University, Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, ShanDong, P.R.China.
authors.forename: Min
authors.initials: M
authors.lastname: Pang
authors.affiliation: Key Laboratory of Tumor Molecular Biology in Binzhou Medical University, Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, ShanDong, P.R.China.
authors.forename: Jin-Xia
authors.initials: JX
authors.lastname: Hu
authors.affiliation: Key Laboratory of Tumor Molecular Biology in Binzhou Medical University, Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, ShanDong, P.R.China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Chest Surgery, YanTaiShan Hospital, YanTai, ShanDong, P.R.China.
authors.forename: Ning
authors.initials: N
authors.lastname: Xie
authors.affiliation: Key Laboratory of Tumor Molecular Biology in Binzhou Medical University, Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, ShanDong, P.R.China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Tumor Molecular Biology in Binzhou Medical University, Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, ShanDong, P.R.China.
authors.forename: Ping-Yu
authors.initials: PY
authors.lastname: Wang
authors.affiliation: Key Laboratory of Tumor Molecular Biology in Binzhou Medical University, Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, ShanDong, P.R.China.
authors.forename: Shu-Yang
authors.initials: SY
authors.lastname: Xie
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009857:Oncogenes; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D051900:Smad3 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C546087:MIRN206 microRNA, human; D035683:MicroRNAs; C544302:Mirn140 microRNA, human; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C489044:TRIB2 protein, human