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Oncotarget. 2016 Apr 12;7(15):20728-42. doi: 10.18632/oncotarget.8011.

MicroRNA-137 inhibits tumor growth and sensitizes chemosensitivity to paclitaxel and cisplatin in lung cancer.

Shen H1,2, Wang L3,4,2, Ge X3,4,2, Jiang CF3,4,2, Shi ZM5,2, Li DM3,4,2, Liu WT3,4,2, Yu X6, Shu YQ1,2.

Author information

1
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
2
Collaborative Innovation Center for Cancer Medicine, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
3
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
4
Department of Pathology, and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
5
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
6
Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Minhang, Shanghai, 200080, China.

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.

KEYWORDS:

NUCKS1; chemosensitivity; cisplatin; miR-137; paclitaxel

PMID:
26989074
PMCID:
PMC4991488
DOI:
10.18632/oncotarget.8011
[Indexed for MEDLINE]
Free PMC Article

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