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

Aging (Albany NY). 2021 Jul 2;13(13):17285-17301. doi: 10.18632/aging.203209. Epub 2021 Jul 2.

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.

Keywords: HSP90AA1; ZNRD1-AS1; competitive endogenous RNA; gastric cancer; miR-9-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Knockdown Techniques
  • HSP90 Heat-Shock Proteins / genetics*
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Metastasis / genetics*
  • RNA, Antisense / genetics*
  • Signal Transduction / genetics*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • HSP90 Heat-Shock Proteins
  • HSP90AA1 protein, human
  • Histocompatibility Antigens Class I
  • MIRN92 microRNA, human
  • MicroRNAs
  • RNA, Antisense
  • ZNRD1AS gene product, human