Upregulation of circ_0000142 promotes multiple myeloma progression by adsorbing miR-610 and upregulating AKT3 expression

J Biochem. 2021 Apr 18;169(3):327-336. doi: 10.1093/jb/mvaa106.

Abstract

Circular RNAs (circRNAs) play an important regulatory role in a variety of malignancies. Nevertheless, the role of circ_0000142 in multiple myeloma (MM) and its regulatory mechanism remains largely unknown. Real-time polymerase chain reaction was employed to detect the expressions of circ_0000142 and miR-610 in MM tissues and cell lines. The expression of AKT3 and apoptosis-related proteins (Bcl-2, Bax) in MM cells was detected by western blot. The correlation between the expression level of circ_0000142 and the clinicopathological parameters of MM patients was analysed. Cell proliferation, apoptosis, migration and invasion were monitored by Cell Counting Kit 8 assay, flow cytometry analysis and Transwell assay, respectively. The dual-luciferase reporter gene assay and RNA immunoprecipitation assay were employed to verify the targeting relationship between circ_0000142 and miR-610. In this study, it was demonstrated that, circ_0000142 was highly expressed in MM patients, and its high expression level was significantly associated with increased International Staging System and Durie-Salmon stage. Overexpression of circ_0000142 enhanced MM cell proliferation, migration, invasion and suppressed cell apoptosis, while knocking down circ_0000142 had the opposite effects. Mechanistically, circ_0000142 functioned as a competitive endogenous RNA, directly targeting miR-610 and positively regulating AKT3 expression. In brief, circ_0000142 enhances the proliferation and metastasis of MM cells by modulating the miR-610/AKT3 axis.

Keywords: AKT3; MM; ceRNA; circ_0000142; miR-610.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Multiple Myeloma / genetics
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Real-Time Polymerase Chain Reaction / methods
  • Up-Regulation

Substances

  • MIRN610 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Circular
  • AKT3 protein, human
  • Proto-Oncogene Proteins c-akt