Targeting the miR-6734-3p/ZEB2 axis hampers development of non-small cell lung cancer (NSCLC) and increases susceptibility of cancer cells to cisplatin treatment

靶向 miR-6734-3p/ZEB2 轴可阻碍非小细胞肺癌 (NSCLC) 的发展并增加癌细胞对顺铂治疗的敏感性

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作者:Linying Wei, Jianyang Jiang

Abstract

The unclear pathogenesis mechanisms and resistance of cancer cells to chemical drugs serious limits the development of effective treatment strategies for non-small cell lung cancer (NSCLC). In this study, we managed to investigate this issue, and identify potential cancer associated biomarkers for NSCLC diagnosis, prognosis and treatment. This study found that miR-6734-3p was downregulated in both NSCLC clinical specimens (tissues and serum) and cells, compared to the normal tissues and cells. Next, upregulation of miR-6734-3p inhibited cancer formation and progression in NSCLC cells in vitro and in vivo. Conversely, miR-6734-3p ablation had opposite effects and facilitated NSCLC development. In addition, miR-6734-3p bound to the 3' untranslated region (3'UTR) of zinc finger E-box binding homeobox 2 (ZEB2) mRNA to suppress its expressions in NSCLC cells. Interestingly, the inhibiting effects of miR-6734-3p overexpression on NSCLC progression were abrogated by upregulating ZEB2. Furthermore, both upregulated miR-6734-3p and silencing of ZEB2 increased cisplatin-sensitivity in cisplatin-resistant NSCLC (CR-NSCLC) cells. Taken together, miR-6734-3p played an anti-tumor role to hinder cancer development and enhanced the cytotoxic effects of cisplatin treatment on NSCLC cells by downregulating ZEB2.

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