LncRNA GAS6-AS2 promotes bladder cancer proliferation and metastasis via GAS6-AS2/miR-298/CDK9 axis

J Cell Mol Med. 2019 Feb;23(2):865-876. doi: 10.1111/jcmm.13986. Epub 2018 Nov 5.

Abstract

Long noncoding RNAs (lncRNAs) have been proved to play important roles in carcinogenesis and development of numerous cancers, but their biological functions in bladder cancer remain largely unknown. In this study, a novel lncRNA termed GAS6-AS2 were primary identified, and its roles as well as mechanisms in regulating proliferation and metastasis of bladder cancer cells were investigated. Clinically, GAS6-AS2 was significantly up-regulated in bladder cancer tissues and positively correlated with tumour stages and poor prognosis. Moreover, expression of GAS6-AS2 was also increased in bladder cancer cells compared with normal bladder cells. Further investigating the roles of GAS6-AS2, we found GAS6-AS2 regulated proliferation and proliferative activity of bladder cancer cells via inducing G1 phase arrest. What's more, we found that GAS6-AS2 contributed to metastatic abilities of cells. In mechanism, GAS6-AS2 could function as a competitive endogenous RNA (ceRNA) via direct sponging miR-298, which further regulating the expression of CDK9. Finally, we also proved that GAS6-AS2 knockdown suppressed tumour growth and metastasis in vivo. In conclusion, our study proved that GAS6-AS2 could function as a ceRNA and promote the proliferation and metastasis of bladder cancer cells, which provided a novel prognostic marker for bladder cancer patients in clinic.

Keywords: GAS6-AS2; bladder cancer; metastasis; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Pairing
  • Base Sequence
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Cyclin-Dependent Kinase 9 / genetics*
  • Cyclin-Dependent Kinase 9 / metabolism
  • Female
  • G1 Phase Cell Cycle Checkpoints / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Lung Neoplasms / secondary
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Survival Analysis
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Intercellular Signaling Peptides and Proteins
  • MIRN298 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • growth arrest-specific protein 6
  • CDK9 protein, human
  • Cyclin-Dependent Kinase 9