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A micRNA-200c/cathepsin L feedback loop determines paclitaxel resistance in human lung cancer A549 cells in vitro through regulating epithelial-mesenchymal transition.

Research paper by Yi-Fan YF Zhao, Mei-Ling ML Han, Ya-Jie YJ Xiong, Long L Wang, Yao Y Fei, Xiao X Shen, Ying Y Zhu, Zhong-Qin ZQ Liang

Indexed on: 09 Dec '17Published on: 09 Dec '17Published in: Acta Pharmacologica Sinica



Abstract

Cathepsin L (CTSL), a cysteine protease, is closely related to tumor occurrence, development, and metastasis, and possibly regulates cancer cell resistance to chemotherapy. miRNAs, especially the miR-200 family, have been implicated in drug-resistant tumors. In this study we explored the relationship of CTSL, micRNA-200c and drug resistance, and the potential regulatory mechanisms in human lung cancer A549 cells and A549/TAX cells in vitro. A549/TAX cells were paclitaxel-resistant A549 cells overexpressing CTSL and characterized by epithelial-mesenchymal transition (EMT). We showed that micRNA-200c and CTSL were reciprocally linked in a feedback loop in these cancer cells. Overexpression of micRNA-200c in A549/TAX cells decreased the expression of CTSL, and enhanced their sensitivity to paclitaxel and suppressed EMT, whereas knockdown of micRNA-200c in A549 cells significantly increased the expression of CTSL, and decreased their sensitivity to paclitaxel and induced EMT. Overexpression of CTSL in A549 cells significantly decreased the expression of micRNA-200c, and reduced their sensitivity to paclitaxel and induced EMT, but these effects were reversed by micRNA-200c, whereas knockdown of CTSL in A549/TAX cells attenuated paclitaxel resistance and remarkably inhibited EMT, but the inhibition of micRNA-200c could reverse these effects. Therefore, micRNA-200c may be involved in regulating paclitaxel resistance through CTSL-mediated EMT in A549 cells, and CTSL and micRNA-200c are reciprocally linked in a feedback loop.