Oncotarget

Research Papers:

MicroRNA-630 may confer favorable cisplatin-based chemotherapy and clinical outcomes in non-small cell lung cancer by targeting Bcl-2

Ming-Jenn Chen, De-Wei Wu, Gao-Chang Wang, Yao-Chen Wang, Chi-Yi Chen and Huei Lee _

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Oncotarget. 2018; 9:13758-13767. https://doi.org/10.18632/oncotarget.24474

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Abstract

Ming-Jenn Chen1,2,*, De-Wei Wu3,*, Gao-Chang Wang3, Yao-Chen Wang4,6, Chi-Yi Chen5,6 and Huei Lee3

1Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan, ROC

2Department of Sports Management, College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan, ROC

3Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan, ROC

4Department of Internal Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC

5Department of Surgery, Chung Shan Medical University, Taichung, Taiwan, ROC

6School of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC

*These authors contributed equally to this work

Correspondence to:

Huei Lee, email: hl@tmu.edu.tw

Keywords: Micro-630; Bcl-2; cisplatin; chemotherapy; NSCLC

Received: July 26, 2017     Accepted: February 03, 2018     Published: February 09, 2018

ABSTRACT

MicroRNA-630 (miR-630) plays dual roles in tumor progression in various human cancers. However, the role of miR-630 in chemoresistance and prognosis in non-small cell lung cancer (NSCLC) remains to be elucidated. This retrospective study enrolled 114 surgically resected patients with NSCLC who experienced tumor relapse and underwent cisplatin-based chemotherapy. The aim was to examine the possible association between miR-630 (and its targeting of Bcl-2 expression) and the response to cisplatin-based chemotherapy. Patients with tumors expressing low miR-630, high Bcl-2, and a combination of both were more likely than their counterparts to show unfavorable responses to cisplatin-based chemotherapy. Kaplan–Meier and Cox regression analysis indicated that low miR-630, high Bcl-2, and a combination of both may independently predict poor overall survival and short relapse-free survival in patients with NSCLC. Six types of NSCLC cells were collected to determine the inhibitory concentration of cisplatin yielding 50% viability (IC50) by the MTT assay. The IC50 value for cisplatin was negatively correlated with miR-630 expression levels among these cell types, except for A549 cells. Mechanistically, low miR-630 expression conferred cisplatin resistance and colony formation by de-targeting Bcl-2 in NSCLC cells. We therefore suggest that low miR-630, high Bcl-2, and a combination of both may potentially predict an unfavorable chemotherapeutic response and poor outcome in patients with NSCLC.


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