USF1-mediated upregulation of lncRNA GAS6-AS2 facilitates osteosarcoma progression through miR-934/BCAT1 axis

Aging (Albany NY). 2020 Apr 8;12(7):6172-6190. doi: 10.18632/aging.103015. Epub 2020 Apr 8.

Abstract

Long noncoding RNAs (lncRNAs) have been certified as important regulators in tumorigenesis. LncRNA GAS6-AS2 (GAS6-AS2) was a newly identified tumor-related lncRNA, and its dysregulation and oncogenic effects in melanoma and bladder cancer had been reported in previous studies. However, the expression pattern and potential function of GAS6-AS2 in osteosarcoma (OS) have not been investigated. In this study, we identified a novel OS-related lncRNA GAS6-AS2. We found that GAS6-AS2 was distinctly upregulated in both OS specimens and cell lines. Distinct up-regulation of GAS6-AS2 in OS was correlated with advanced clinical stages and shorter survivals. In addition, USF1 could directly bind to the GAS6-AS2 promoter and contribute to its overexpression. Furthermore, GAS6-AS2 knockdown caused tumor suppressive effects via reducing cellular proliferation, migration and invasion, and promoting OS cell apoptosis. Besides, GAS6-AS2 directly bound to miR-934 and downregulated its expression. Mechanistically, GAS6-AS2 positively regulated the expression of BCAT1 through sponging miR-934. Taken together, our data illustrated how GAS6-AS2 played an oncogenic role in OS and might offer a potential therapeutic target for treating OS.

Keywords: BCAT1; GAS6-AS2; USF1; miR-934; osteosarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • MicroRNAs / metabolism*
  • Osteosarcoma* / genetics
  • Osteosarcoma* / pathology
  • RNA, Long Noncoding / metabolism*
  • Transaminases / metabolism
  • Transcriptional Activation
  • Up-Regulation
  • Upstream Stimulatory Factors / metabolism*

Substances

  • Intercellular Signaling Peptides and Proteins
  • MIRN934 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • USF1 protein, human
  • Upstream Stimulatory Factors
  • growth arrest-specific protein 6
  • BCAT1 protein, human
  • Transaminases