title: MiR-181b regulates cisplatin chemosensitivity and metastasis by targeting TGFβR1/Smad signaling pathway in NSCLC.
abstract: MicroRNAs (miRNAs) have been identified as important post-transcriptional regulators involved in various biological and pathological processes of cells, but their underlying mechanisms in chemosensitivity and metastasis have not been fully elucidated. The objective of this study was to identify miR-181b and its mechanism in the chemosensitivity and metastasis of NSCLC. We found that miR-181b expression levels were lower in A549/DDP cells compared with A549 cells. Functional assays showed that the overexpression of miR-181b inhibited proliferation, enhanced chemosensitivity to DDP, attenuated migration and metastatic ability in NSCLC cell lines in vitro and in vivo. TGFβR1 was subsequently identified as a novel functional target of miR-181b. TGFβR1 knockdown revealed similar effects as that of ectopic miR-181b expression, whereas overexpression of TGFβR1 rescued the function of miR-181b-mediated growth, chemosensitivity and metastasis in NSCLC cells. In addition, miR-181b could inactivate the TGFβR1/Smad signaling pathway. We also observed that decreased miR-181b expression and increased TGFβR1 expression were significantly associated with chemosensitivity to DDP and tumor metastasis in NSCLC patients. Consequently, miR-181b functions as a tumor suppressor and has an important role in proliferation, chemosensitivity to DDP and metastasis of NSCLC by targeting TGFβR1/Smad signaling pathway.
authors.affiliation: Department of Internal Medical Oncology, Harbin medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Internal Medical Oncology, Harbin medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Internal Medical Oncology, Harbin medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Internal Medical Oncology, Harbin medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Jing
authors.affiliation: Department of Internal Medical Oncology, Harbin medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
authors.forename: Hailing
authors.initials: H
authors.lastname: Lu
authors.affiliation: Cancer Research Institute, Harbin Medical University, Harbin, Heilongjiang Province, China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Internal Medical Oncology, Harbin medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Internal Medical Oncology, Harbin medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D002945:Cisplatin