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, miRNA-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 miRNA-200c and CTSL were reciprocally linked in a feedback loop in these cancer cells. Overexpression of miRNA-200c in A549/TAX cells decreased the expression of CTSL, and enhanced their sensitivity to paclitaxel and suppressed EMT, whereas knockdown of miRNA-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 miRNA-200c, and reduced their sensitivity to paclitaxel and induced EMT, but these effects were reversed by miRNA-200c, whereas knockdown of CTSL in A549/TAX cells attenuated paclitaxel resistance and remarkably inhibited EMT, but the inhibition of miRNA-200c could reverse these effects. Therefore, miRNA-200c may be involved in regulating paclitaxel resistance through CTSL-mediated EMT in A549 cells, and CTSL and miRNA-200c are reciprocally linked in a feedback loop.

中文翻译：

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miRNA-200c / cathepsin L反馈环通过调节上皮-间质转化来确定人肺癌A549细胞在体外的紫杉醇耐药性。

组织蛋白酶L（CTSL）是一种半胱氨酸蛋白酶，与肿瘤的发生，发展和转移密切相关，并可能调节癌细胞对化学疗法的抵抗力。miRNA，特别是miR-200家族，与耐药性肿瘤有关。在这项研究中，我们探讨了CTSL，miRNA-200c与耐药性之间的关系，以及在体外对人肺癌A549细胞和A549 / TAX细胞的潜在调控机制。A549 / TAX细胞是抗紫杉醇的A549细胞，过度表达CTSL，并具有上皮-间质转化（EMT）的特征。我们显示，miRNA-200c和CTSL在这些癌细胞的反馈回路中相互连接。miRNA-200c在A549 / TAX细胞中的过表达降低了CTSL的表达，并增强了其对紫杉醇的敏感性并抑制了EMT，而在A549细胞中敲除miRNA-200c则显着增加CTSL的表达，并降低其对紫杉醇和诱导EMT的敏感性。A549细胞中CTSL的过表达显着降低了miRNA-200c的表达，并降低了其对紫杉醇和诱导的EMT的敏感性，但这些作用被miRNA-200c所逆转，而敲除A549 / TAX细胞中的CTSL则减弱了紫杉醇的耐药性，并显着抑制了它的表达。 EMT，但抑制miRNA-200c可以逆转这些作用。因此，miRNA-200c可能通过A549细胞中CTSL介导的EMT参与调节紫杉醇耐药性，并且CTSL和miRNA-200c在反馈回路中相互连接。A549细胞中CTSL的过表达显着降低了miRNA-200c的表达，并降低了其对紫杉醇和诱导的EMT的敏感性，但这些作用被miRNA-200c所逆转，而敲除A549 / TAX细胞中的CTSL则减弱了紫杉醇的耐药性，并显着抑制了它的表达。 EMT，但抑制miRNA-200c可以逆转这些作用。因此，miRNA-200c可能通过A549细胞中CTSL介导的EMT参与调节紫杉醇耐药性，并且CTSL和miRNA-200c在反馈回路中相互连接。A549细胞中CTSL的过表达显着降低了miRNA-200c的表达，并降低了其对紫杉醇和诱导的EMT的敏感性，但这些作用被miRNA-200c所逆转，而敲除A549 / TAX细胞中的CTSL则减弱了紫杉醇的耐药性，并显着抑制了它的表达。 EMT，但抑制miRNA-200c可以逆转这些作用。因此，miRNA-200c可能通过A549细胞中CTSL介导的EMT参与调节紫杉醇耐药性，并且CTSL和miRNA-200c在反馈回路中相互连接。但是抑制miRNA-200c可以逆转这些作用。因此，miRNA-200c可能通过A549细胞中CTSL介导的EMT参与调节紫杉醇耐药性，并且CTSL和miRNA-200c在反馈回路中相互连接。但是抑制miRNA-200c可以逆转这些作用。因此，miRNA-200c可能通过A549细胞中CTSL介导的EMT参与调节紫杉醇耐药性，并且CTSL和miRNA-200c在反馈回路中相互连接。