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Int J Clin Exp Med. 2015 Aug 15;8(8):12397-403. eCollection 2015.

MicroRNA 192 regulates chemo-resistance of lung adenocarcinoma for gemcitabine and cisplatin combined therapy by targeting Bcl-2.

Author information

1
Department of Interventional Oncology, Dahua Hospital Xuhui District, Shanghai 200237,China ; College of Medicine, Soochow University Suzhou, 215123, China.
2
Department of Interventional Oncology, Dahua Hospital Xuhui District, Shanghai 200237,China.
3
Department of Radiology, The Affiliated Sixth People's Hospital of Shanghai Jiao Tong University Yi Shan Road 600, Shanghai 200233, China.

Abstract

Lung cancer is the most leading cause of cancer-related death worldwide, with non-small-cell lung cancer (NSCLC) accounting for over 80% of all lung cancer cases. Patients with NSCLC are mostly treated with platinum-based chemotherapy. Chemoresistance is a leading cause of chemo-therapy failure in NSCLC treatment. Recent studies have shown that dysregulation of microRNAs might modulate the resistance of cancer cells to anti-cancer drugs, yet the modulation mechanism is not fully understood. In this paper, we try to test whether miR-192 regulates chemo-resistance in human carcinoma A549 mice model by targeting Bcl-2. Mice model of human lung adenocarcinoma was built up, and was used for gemcitabine and cisplatin combined chemotherapy. MTT assay, real-time RT-PCR, western blotting assay were used to investigate miR-192 expression levels, cell viability ratio and Bcl-2 protein expression levels. MiR-192 expression level in A549 cells is significantly higher than in normal human bronchial epithelial cells. MiR-192 inhibitor treated tumor exhibits sensitivity to cisplatin and gemcitabine therapy. Bcl-2 mRNA and protein expression levels up-regulated in miR-192 inhibitor treated tumor. Bcl-2 is a key regulator for miR-192 related chemotherapy resistance. In this study, we demonstrate that miR-192 regulates chemoresistance for gemcitabine and cisplatin combined chemotherapy in human adenocarcinoma lung cancer A549 cells, and Bcl-2 is the target of miR-192.

KEYWORDS:

Bcl-2; MicroRNA; chemoresistance; pathways

PMID:
26550150
PMCID:
PMC4612835

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