Circ_0000467 modulates malignant characteristics of colorectal cancer via sponging miR-651-5p and up-regulating DNMT3B

Nucleosides Nucleotides Nucleic Acids. 2023;42(2):134-150. doi: 10.1080/15257770.2022.2112050. Epub 2022 Sep 6.

Abstract

Circular RNAs (circRNAs) are widely expressed in cancer tissues and participate in modulating the progression of malignant tumors, playing a pro- or anti-cancer role. This work is conducted to probe the precise role of circ_0000467 in colorectal cancer (CRC) and its regulatory mechanism. The differentially expressed circRNAs in CRC tissues and paracancerous tissues were screened by bioinformatics analysis. The expression levels of circ_0000467, miR-651-5p and DNA methyltransferases 3B (DNMT3B) mRNA in CRC tissues and cells were detected by qRT-PCR. circ_0000467 knockdown cell model was constructed to investigate the effects of circ_0000467 on CRC cell growth, migration and invasion by CCK-8 and Transwell experiments. Western blot was performed to examine DNMT3B protein expression in CRC cells. Dual-luciferase reporter gene experiment was executed to validate the targeting relationship between circ_0000467 and miR-651-5p, miR-651-5p and DNMT3B. Circ_0000467 expression and DNMT3B mRNA expression were increased and miR-651-5p expression was down-regulated in CRC tissues and cell lines. Knockdown of circ_0000467 repressed CRC cell growth, migration and invasion. Dual-luciferase reporter gene experiments validated that miR-651-5p was a direct target of circ_0000467 and miR-651-5p could specifically bind with DNMT3B 3'UTR. Functional compensation experiments showed that the regulatory effect of circ_0000467 on CRC cells' behaviors could be partially counteracted by miR-651-5p. Circ_0000467 may enhance the growth and metastasis of CRC cells by targeting miR-651-5p and up-regulating DNMT3B expression. Circ_0000467 may be a potential diagnostic biomarker and therapeutic target for CRC.

Keywords: CRC; DNMT3B; circ_0000467; miR-651-5p.

MeSH terms

  • 3' Untranslated Regions
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms* / genetics
  • Genes, Reporter
  • Humans
  • MicroRNAs* / genetics
  • RNA, Circular / genetics

Substances

  • RNA, Circular
  • 3' Untranslated Regions
  • MicroRNAs