Abstract 3065: MicroRNA-137 confers chemoresistance by suppressing CASP3 in lung cancer cells

Autor: Te-Jen Shu, Sung-Liang Yu, Jeremy J.W. Chen
Rok vydání: 2015
Předmět:
Zdroj: Cancer Research. 75:3065-3065
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am2015-3065
Popis: Lung cancer is the leading cause of cancer-related death. Although molecular targeting therapy (MTT) could benefit patients with EGFR activating mutations, chemotherapy still is the first choice of EGFR wild type patients, MTT failed ones and patients of developing countries without regarding their EGFR status. However most of these chemotherapy-treated patients will develop drug resistance eventually. Here, we identified miR-137 might contribute to chemo-resistance in lung cancer in part. Our previous study identified 5 miRNAs (let-7a, miR-182*, miR-372, miR-137 and miR-221) whose expression can be an independent marker to predict the outcome of non-small cell lung cancer (NSCLC) patients. Among them, miR-137 acts as a risky miRNA. Caspase-3 (CASP3) was predicted as one of miR-137 potential targets. CASP3 is a critical effector caspase that promotes programmed cell-death when activated in the apoptotic cells both by extrinsic and intrinsic pathways that are highly conserved and related to drug resistance. We found miR-137 could regulate CASP3 through binding to its 3′UTR. Endogenous CASP3 can be up-regulated by over-expressing miR 137 in CL1-5, H1437 and A549 cells and down-regulated by silencing miR-137 in H1299, CL1-0 and A549 cells. Suppression of CASP3 by miR-137 providing lung cancer cells with ability of anti-apoptosis under UV-induced cell death. MiR-137 also increase IC50 of CL1-5, H1437, A549 and H1975 cells under cisplatin treatment to at least 2 folds. Restoration of CASP3 could reverse the effect. Our IHC data also shows the CASP3 protein expression is negative correlated with miR-137 level. In summary, manipulation of miR-137 might provide a potential treatment for EGFR wild-type and MTT failed NSCLC. patients in the future. Citation Format: Te-Jen Shu, Sung-Liang Yu, Jeremy J.W. Chen. MicroRNA-137 confers chemoresistance by suppressing CASP3 in lung cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3065. doi:10.1158/1538-7445.AM2015-3065
Databáze: OpenAIRE
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