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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.01103

LncRNA AFAP1-AS1 supresses miR-139-5p and promotes cell proliferation and chemotherapy resistance of non-small cell lung cancer by competitively upregulating RRM2

 Wei Guo1, Ke Ren1, Na Huang1, Yi Jiang1, Jian Sun1, Wenjing Dai1, Wancheng Li1 and  Wei Zhao1*
  • 1Chengdu Medical College, China

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. This study aims to understand the underlying mechanism of lncRNA, actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1) in mediating chemotherapeutic resistance in NSCLC. The levels of AFAP1-AS1 in NSCLC tissues and cells were determined using RT- PCR. The protein levels of RRM2, EGFR and p-AKT were analysed using Western blotting. Binding between AFAP1-AS1 and miR-139-5p was confirmed using dual luciferase reporter and RNA immunoprecipitation (RIP) assays, and binding between miR-139-5p and RRM2 was confirmed by a dual luciferase reporter assay. NSCLC cell proliferation, apoptosis, and colony formation were examined using MTT, flow cytometry, and colony formation assays, respectively. It was found that AFAP1-AS1 expression was upregulated in NSCLC tissues and cells. In addition, AFAP1-AS1 bound to and downregulated the expression of miR-139-5p, which was reduced in NSCLC tissues. Knockdown of AFAP1-AS1 and overexpression of miR-139-5p inhibited NSCLC cell proliferation, colony formation and chemotherapy resistance and increased cell apoptosis. Additionally, AFAP1-AS1 upregulates RRM2 expression via sponging miR-139-5p. Furthermore, AFAP1-AS1 enhanced NSCLC cell proliferation and chemotherapy resistance through upregulating RRM2 by inhibiting miR-139-5p expression. Moreover, RRM2 promoted cellular chemotherapy resistance by activating EGFR/AKT. Finally, knockdown of AFAP1-AS1 significantly suppressed tumour growth and chemoresistance in nude mice. In conclusion, AFAP1-AS1 promoted chemotherapy resistance by supressing miR-139-5p expression and promoting RRM2/EGFR/AKT signalling pathway in NSCLC cells.

Keywords: AFAP1-AS1, miR-139-5p, RRM2, Non-small cell lung cancer, EGFR/Akt

Received: 05 Aug 2019; Accepted: 07 Oct 2019.

Copyright: © 2019 Guo, Ren, Huang, Jiang, Sun, Dai, Li and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Wei Zhao, Chengdu Medical College, Chengdu, Sichuan, China,