Circular RNA hsa_circ_0053277 promotes the development of colorectal cancer by upregulating matrix metallopeptidase 14 via miR-2467-3p sequestration

J Cell Physiol. 2020 Mar;235(3):2881-2890. doi: 10.1002/jcp.29193. Epub 2019 Sep 24.

Abstract

Colorectal cancer (CRC), a kind of human gastrointestinal cancer, has been reported to be one of the most common malignant tumors worldwide. Increasing evidence has indicated that circular RNAs exert significant effects on the development of multiple cancers. Nevertheless, whether hsa_circ_0053277 regulates the progression of CRC remains to be explored. In this study, our results showed that the expression of hsa_circ_0053277 was markedly upregulated in CRC tissues and cells. Knockdown of hsa_circ_0053277 inhibited cell proliferation, migration, and epithelial-mesenchymal transition (EMT) process in CRC. miR-2467-3p had a binding site for hsa_circ_0053277. Molecular mechanism assays confirmed that hsa_circ_0053277 could bind with miR-2467-3p. In addition, hsa_circ_0053277 accelerated cell proliferation rate by acting as a sponge for miR-2467-3p in CRC. Matrix metalloproteinase 14 (MMP14) expression was notably upregulated in CRC cells and MMP14 was a downstream target gene of miR-2467-3p. Besides, hsa_circ_0053277 positively regulated MMP14 expression while miR-2467-3p negatively regulated MMP14 expression. Rescue assays verified that MMP14 knockdown countervailed the function of miR-2467-3p inhibitor on cell proliferation, migration, and EMT process in CRC. To sum up, hsa_circ_0053277 facilitated the development of CRC by sponging miR-2467-3p to upregulate MMP14 expression.

Keywords: CRC; MMP14; hsa_circ_0053277; miR-2467-3p.

MeSH terms

  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colonic Neoplasms / genetics
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Knockdown Techniques / methods
  • Humans
  • Matrix Metalloproteinase 14 / genetics*
  • MicroRNAs / genetics*
  • RNA, Circular / genetics*
  • Up-Regulation

Substances

  • MIRN2467 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • MMP14 protein, human
  • Matrix Metalloproteinase 14