A1BG-AS1 promotes the biological functions of osteosarcoma cells via regulating the microRNA-148a-3p/USP22 axis and stabilizing the expression of SIRT1 through deubiquitinase function

Expert Opin Ther Targets. 2023 Jul-Dec;27(10):1017-1029. doi: 10.1080/14728222.2023.2263908. Epub 2023 Oct 30.

Abstract

Background: The study aims to explore the role of A1BG antisense RNA 1 (A1BG-AS1), microRNA (miR)-148a-3p and ubiquitin-specific protease 22 (USP22) on osteosarcoma (OS) cell growth.

Research design & methods: A1BG-AS1, miR-148a-3p, USP22, and silent information regulator 2 homolog 1 (SIRT1) levels in OS tissues and cells were determined. The effects of A1BG-AS1, miR-148a-3p, and USP22 on the biological functions of OS cells were examined by functional assays. In vivo assay was conducted to observe the effect of A1BG-AS1 on OS growth in vitro. The relationship of A1BG-AS1, miR-148a-3p, and USP22 was analyzed by bioinformatics analysis, RNA-fluorescence in situ hybridization, luciferase activity, and RNA binding protein immunoprecipitation assays. The relation between USP22 and SIRT1 was evaluated by immunoprecipitation.

Results: A1BG-AS1 and USP22 were highly expressed, and miR-148a-3p was lowly expressed in OS tissues and cells. Down-regulation of A1BG-AS1 and USP22 or up-regulation of miR-148a-3p impaired the malignant behaviors of OS cells. A1BG-AS1 sponged miR-148a-3p, and miR-148a-3p targeted USP22, thereby inhibiting USP22 expression. Up-regulating USP22 reversed the A1BG-AS1 suppression-induced phenotypic inhibition of OS cells. USP22 affected the biological functions of OS cells by deubiquitinating SIRT1.

Conclusion: A1BG-AS1 facilitates the biological functions of OS cells via mediating the miR-148a-3p/USP22 axis.

Keywords: Osteosarcoma; deubiquitination; long non-coding RNA A1BG antisense RNA 1; microRNA-148a-3p; silent information regulator 2 homolog 1; ubiquitin-specific protease 22.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Deubiquitinating Enzymes / genetics
  • Deubiquitinating Enzymes / metabolism
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Humans
  • Immunoglobulins / genetics
  • Immunoglobulins / metabolism
  • In Situ Hybridization, Fluorescence
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Osteosarcoma* / genetics
  • Osteosarcoma* / metabolism
  • Osteosarcoma* / pathology
  • RNA, Long Noncoding* / genetics
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism

Substances

  • MicroRNAs
  • Sirtuin 1
  • Deubiquitinating Enzymes
  • RNA, Long Noncoding
  • A1BG protein, human
  • Glycoproteins
  • Immunoglobulins
  • SIRT1 protein, human