title: MicroRNA-137 inhibits tumor growth and sensitizes chemosensitivity to paclitaxel and cisplatin in lung cancer.
abstract: Chemotherapy resistance frequently drives tumour progression. However, the underlying molecular mechanisms are poorly characterized. In this study, we explored miR-137's role in the chemosensitivity of lung cancer. We found that the expression level of miR-137 is down-regulated in the human lung cancer tissues and the resistant cells strains: A549/paclitaxel(A549/PTX) and A549/cisplatin (A549/CDDP) when compared with lung cancer A549 cells. Moreover, we found that overe-expression of miR-137 inhibited cell proliferation, migration, cell survival and arrest the cell cycle in G1 phase in A549/PTX and A549/CDDP. Furthermore, Repression of miR-137 significantly promoted cell growth, migration, cell survival and cell cycle G1/S transition in A549 cells. We further demonstrated that the tumor suppressive role of miR-137 was mediated by negatively regulating Nuclear casein kinase and cyclin-dependent kinase substrate1(NUCKS1) protein expression. Importantly, miR-137 inhibits A549/PTX, A549/CDDP growth and angiogenesis in vivo. Our study is the first to identify the tumor suppressive role of over-expressed miR-137 in chemosensitivity. Identification of a novel miRNA-mediated pathway that regulates chemosensitivity in lung cancer will facilitate the development of novel therapeutic strategies in the future.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.|Collaborative Innovation Center for Cancer Medicine, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.|Department of Pathology, and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.|Collaborative Innovation Center for Cancer Medicine, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.|Department of Pathology, and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.|Collaborative Innovation Center for Cancer Medicine, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ge
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.|Department of Pathology, and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.|Collaborative Innovation Center for Cancer Medicine, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Cheng-Fei
authors.initials: CF
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.|Collaborative Innovation Center for Cancer Medicine, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Zhu-Mei
authors.initials: ZM
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.|Department of Pathology, and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.|Collaborative Innovation Center for Cancer Medicine, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Li
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.|Department of Pathology, and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.|Collaborative Innovation Center for Cancer Medicine, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Wei-Tao
authors.initials: WT
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Minhang, Shanghai, 200080, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.|Collaborative Innovation Center for Cancer Medicine, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Yong-Qian
authors.initials: YQ
authors.lastname: Shu
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017239:Paclitaxel / Q000008:administration & dosage; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C545567:MIRN137 microRNA, human; D035683:MicroRNAs; C426654:NUCKS1 protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D017239:Paclitaxel; D002945:Cisplatin
keywords: NUCKS1; chemosensitivity; cisplatin; miR-137; paclitaxel