https://scholars.lib.ntu.edu.tw/handle/123456789/147005
Title: | Oncogenic miR-137 contributes to cisplatin resistance via repressing CASP3 in lung adenocarcinoma | Authors: | Su, Te-Jen Ku, Wen-Hui Chen, Hsuan-Yu Hsu, Yi-Chiung Hong, Qi-Sheng Chang, Gee-Chen Yu, Sung-Liang Chen, Jeremy J. W. |
Keywords: | miR-137;lung adenocarcinoma;cisplatin;caspase 3;chemoresistance | Issue Date: | 2016 | Journal Volume: | 6 | Journal Issue: | 6 | Start page/Pages: | 1317-1330 | Source: | Am. J. Cancer Res. | Abstract: | Although targeted therapy can prolong the survival of non-small cell lung cancer (NSCLC) patients with EGFR mutations, chemotherapy still is the choice for patients with wild-type EGFR or failure in targeted therapy. However, most of the patients will eventually develop chemoresistance. Our previous study showed that miR-137 is a risky microRNA and is associated with poor prognosis in NSCLC patients. Here we investigated the role of miR-137 in cisplatin resistance in lung adenocarcinoma patients. Our data indicated that miR-137 overexpression increases the survival of lung cancer cells exposed to cisplatin and decreases cisplatin-induced apoptosis. Through computational prediction and microarray, we identified caspase-3 (CASP3) as a potential target of miR-137. Luciferase reporter and site-directed mutagenesis assays demonstrated that miR-137 downregulates CASP3 through binding to its 3'-UTR. Moreover, the endogenous CASP3 can be modulated by overexpressing or silencing miR-137 in lung adenocarcinoma cell lines regardless of EGFR status. Suppression of CASP3 by miR-137 provides cancer cells with anti-apoptotic ability, leading to cisplatin resistance. Immunohistochemistry results revealed an inverse correlation between miR-137 and CASP3 expressions in lung adenocarcinoma patients. Together, our data provide a new chemoresistance mechanism in lung adenocarcinoma and a possible target to control chemoresistance in lung adenocarcinoma patients. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/280943 |
Appears in Collections: | 醫學檢驗暨生物技術學系 |
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