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. Issue 1 (1st January 2021)

• Record Type: Journal Article
• Authors: Wei, Linying; Jiang, Jianyang
• Is Part Of: Bioengineered. Volume 12:Issue 1(2021)
• Page Start: 2499
• Page End: 2510
• Publication Date: 2021-01-01
• Subjects: Non-small cell lung cancer -- miR-6734-3p -- zinc finger E-box binding homeobox 2 -- cisplatin -- chemosensitivity; Biomedical engineering -- Periodicals; Biotechnology -- Periodicals; Microbiology -- Periodicals; 660.6
• DOI: 10.1080/21655979.2021.1936891
• Languages: English
• ISSNs: 2165-5987

Abstract

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 3ʹ untranslated region (3ʹUTR) 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. Graphical Abstract: uf0001