https://scholars.lib.ntu.edu.tw/handle/123456789/502840
標題: | Oncogenic miR-137 contributes to cisplatin resistance via repressing CASP3 in lung adenocarcinoma | 作者: | Su T.-J. Ku W.-H. Chen H.-Y. Hsu Y.-C. Hong Q.-S. Chang G.-C. SUNG-LIANG YU Chen J.J.W. |
關鍵字: | Caspase 3; Chemoresistance; Cisplatin; Lung adenocarcinoma; MiR-137 | 公開日期: | 2016 | 卷: | 6 | 期: | 6 | 起(迄)頁: | 1317-1330 | 來源出版物: | American Journal of Cancer Research | 摘要: | 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: | https://scholars.lib.ntu.edu.tw/handle/123456789/502840 | ISSN: | 2156-6976 | SDG/關鍵字: | caspase 3; cisplatin; epidermal growth factor receptor; microRNA; microRNA 137; unclassified drug; 3' untranslated region; aged; apoptosis; Article; cancer cell; cancer resistance; cell survival; clinical article; controlled study; down regulation; drug exposure; female; gene function; gene overexpression; genotype; human; human cell; immunohistochemistry; lung adenocarcinoma; male; microarray analysis; protein targeting; site directed mutagenesis |
顯示於: | 醫學檢驗暨生物技術學系 |
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