Knockdown of circRAD23B Exerts Antitumor Response in Colorectal Cancer via the Regulation of miR-1205/TRIM44 axis

Dig Dis Sci. 2022 Feb;67(2):504-515. doi: 10.1007/s10620-021-06859-w. Epub 2021 Feb 25.

Abstract

Background: Colorectal cancer (CRC) is a common cancer with high metastatic property. Circular RNAs (circRNAs) have important involvement in cancer processes. This study focused on the regulation of circRNA RAD23 homologue B (circRAD23B) in CRC.

Methods: The levels of circRAD23B, microRNA-1205 (miR-1205), and tripartite motif-44 (TRIM44) were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Functional analyses were performed by Cell Counting Kit-8 (CCK-8) for cell proliferation, flow cytometry for cell cycle or cell apoptosis, and transwell assay for cell migration and invasion. Western blot was administrated for protein detection. The interaction of targets was analyzed by dual-luciferase reporter and RNA pull-down assays. The in vivo experiment was conducted via xenograft tumor in mice.

Results: We identified that circRAD23B was overexpressed in CRC tissues and cells. CRC cell proliferation, cell cycle progression, and cell metastasis were inhibited, while apoptosis was promoted by downregulating circRAD23B. Target analysis indicated that circRAD23B-targeted miR-1205 and TRIM44 were downstream genes of miR-1205. Moreover, the antitumor response of circRAD23B downregulation and miR-1205 overexpression was, respectively, achieved by increasing miR-1205 and decreasing TRIM44. CircRAD23B could regulate TRIM44 level by sponging miR-1205. In vivo, circRAD23B knockdown also reduced CRC tumorigenesis via the miR-1205/TRIM44 axis.

Conclusion: These results suggested that the inhibition of circRAD23B retarded the progression of CRC via acting on the miR-1205/TRIM44 axis. CircRAD23B might be a novel target in CRC treatment.

Keywords: Colorectal cancer; TRIM44; circRAD23B; miR-1205.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • DNA Repair Enzymes / genetics*
  • DNA-Binding Proteins / genetics*
  • Flow Cytometry
  • Gene Knockdown Techniques
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • RNA, Circular*
  • Real-Time Polymerase Chain Reaction
  • Tripartite Motif Proteins / genetics*

Substances

  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • MIRN1205 microRNA, human
  • MicroRNAs
  • RAD23B protein, human
  • RNA, Circular
  • TRIM44 protein, human
  • Tripartite Motif Proteins
  • DNA Repair Enzymes