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Research Paper|Volume 13, Issue 13|pp 17285—17301

Knockdown of lncRNA ZNRD1-AS1 suppresses gastric cancer cell proliferation and metastasis by targeting the miR-9-5p/HSP90AA1 axis

Ming-Chen Ba1, Zheng Ba2, Yuan-Feng Gong1, Kun-Peng Lin1, Yin-Bing Wu1, Yi-Nuo Tu1
  • 1Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, P.R. China
  • 2Department of Adult Intensive Care Unit, University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, P.R. China
* Equal contribution
Received: December 18, 2020Accepted: June 2, 2021Published: July 2, 2021
https://doi.org/10.18632/aging.203209

Copyright: © 2021 Ba et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

LncRNAs play an important role in a variety of biological processes, such as cancer pathogenesis. The lncRNA zinc ribbon domain containing 1 antisense RNA 1 (ZNRD1-AS1) is a natural antisense transcript of ZNRD1. In this study, we found that ZNRD1-AS1 levels were significantly upregulated in gastric cancer tissues compared to those in adjacent healthy gastric tissues. ZNRD1-AS1 levels were correlated with lymph node metastasis, distal metastasis, and TNM stage, but were not correlated with age and sex. ZNRD1-AS1 knockdown suppressed cell proliferation, migration, and invasion, and promoted apoptosis. ZNRD1-AS1 overexpression had the opposite effect. ZNRD1-AS1 knockdown suppressed tumor growth and pulmonary metastasis in a nude mouse model ZNRD1-AS1 can bind to miR-9-5p and ZNRD1-AS1 knockdown can decrease the protein level of heat shock protein 90 alpha family class A member 1 (HSP90AA1), which is the target of miR-9-5p. The miR-9-5p inhibitor rescued the effect of ZNRD1-AS1 knockdown, and the mutant of miR-9-5p binding site on ZNRD1-AS1 sequence blocked the effect of ZNRD1-AS1 overexpression. In conclusion, ZNRD1-AS1 levels were upregulated in gastric cancer tissues, and knockdown of ZNRD1-AS1 suppressed gastric cancer cell proliferation and metastasis by targeting the miR-9-5p/HSP90AA1 axis. Our findings provide novel insights into the mechanism underlying the role of ZNRD1-AS1 in gastric cancer.