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Research Paper|Volume 11, Issue 15|pp 5705—5725

LncRNA ADAMTS9-AS2 inhibits cell proliferation and decreases chemoresistance in clear cell renal cell carcinoma via the miR-27a-3p/FOXO1 axis

Er-lin Song1, Li Xing2, Liang Wang3, Wen-ting Song4, Dan-bin Li1, Yi Wang1, Yi-wei Gu1, Ming-ming Liu5, Wen-jun Ni1, Peng Zhang6, Xin Ma6, Xu Zhang6, Jie Yao7, Yang Chen8, Rui-hua An1
  • 1Department of Urinary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150007, Heilongjiang Province, P. R. China
  • 2Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin 150007, Heilongjiang Province, P. R. China
  • 3Medical Department, The First Affiliated Hospital of Harbin Medical University, Harbin 150007, Heilongjiang Province, P. R. China
  • 4Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin 150081, Heilongjiang Province, P. R. China
  • 5Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin 150007, Heilongjiang Province, P. R. China
  • 6Department of Urology, Chinese PLA General Hospital/Chinese PLA Medical Academy, Beijing 100036, P.R. China
  • 7Department of Urological Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, P.R. China
  • 8Department of Hematology and Medical Oncology, Beijing ChuiYangLiu Hospital, Beijing 100022, P. R. China
* Equal contribution
Received: June 11, 2019Accepted: August 3, 2019Published: August 10, 2019
https://doi.org/10.18632/aging.102154

Copyright © 2019 Song et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Accumulating evidence reveals the principal role of long noncoding RNAs in the progression of clear cell renal cell carcinoma (ccRCC). However, little is known about the underlying mechanism of ADAM metallopeptidase with thrombospondin type 1 motif, 9 antisense RNA 2 (ADAMTS9-AS2) in ccRCC. Here, bioinformatics analyses verified ADAMTS9-AS2 is a long noncoding RNA and its high expression was associated with better prognosis of ccRCC. ADAMTS9-AS2 was clearly downregulated in ccRCC clinical samples and cell lines. Clinical data showed low-expressed ADAMTS9-AS2 was correlated with worse overall survival in ccRCC patients. Next, miR-27a-3p was identified as an inhibitory target of ADAMTS9-AS2 by dual-luciferase reporter and RNA immunoprecipitation assays. Both overexpressed ADAMTS9-AS2 and underexpressed miR-27a-3p in ccRCC cell lines led to the inhibition of cell proliferation and the reduction of chemoresistance. Additionally, Forkhead Box Protein O1 (FOXO1) was confirmed as the inhibitory target of miR-27a-3p. Induced by ADAMTS9-AS2 overexpression, cell proliferation and chemoresistance exhibited an obvious reduction, FOXO1 expression showed an evident increase, but all were reversed after miR-27a-3p was simultaneously overexpressed. Collectively, these results suggest ADAMTS9-AS2 inhibits the progression and impairs the chemoresistance of ccRCC via miR-27a-3p-mediated regulation of FOXO1 and may serve as a prognostic biomarker and therapeutic target for ccRCC.