Circ_0003489 facilitates multiple myeloma progression by targeting miR-433-3p/PBX3 axis

Hematology. 2022 Dec;27(1):951-959. doi: 10.1080/16078454.2022.2109554.

Abstract

Background: Multiple myeloma (MM) is a relatively common hematologic tumor, and the study of non-coding RNAs in MM is gradually increasing. Our study aimed to reveal the regulatory mechanism of circular RNA_0003489 (circ_0003489)/microRNA-433-3p (miR-433-3p)/Pre-B-cell leukemia homeobox 3 (PBX3) axis in MM.

Methods: Circ_0003489, miR-433-3p and PBX3 contents were measured by real-time quantitative PCR or western blot. Functionally, MM cell proliferation and apoptosis were evaluated using cell counting kit-8, flow cytometry and EdU assays. Interaction between miR-433-3p and circ_0003489 or PBX3 was confirmed with the application of dual-luciferase reporter assay and RNA pull down assay.

Results: Circ_0003489 and PBX3 were upregulated, while miR-433-3p was downregulated in MM tissues. Circ_0003489 knockdown or miR-433-3p overexpression remarkably suppressed MM proliferation and increased apoptosis in vitro. In terms of mechanism, circ_0003489 could sponge miR-433-3p to regulate PBX3. Besides, miR-433-3p downregulation or PBX3 overexpression reversed the inhibition effect of circ_0003489 knockdown on MM progression.

Conclusion: Circ_0003489 facilitated MM progression by targeting miR-433-3p/PBX3 axis, suggesting that it might be a potential target for MM.

Keywords: Circ_0003489; PBX3; miR-433-3p; multiple myeloma.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / metabolism
  • Humans
  • MicroRNAs* / genetics
  • Multiple Myeloma* / genetics
  • Proto-Oncogene Proteins / metabolism
  • RNA, Circular / genetics

Substances

  • Homeodomain Proteins
  • MIRN433 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins
  • RNA, Circular
  • proto-oncogene protein Pbx3