CircMYC promotes proliferation, migration, invasion and inhibits apoptosis of small cell lung cancer by targeting miR-145/ Matrix Metallopeptidase 2 axis

Bioengineered. 2022 Apr;13(4):10552-10563. doi: 10.1080/21655979.2022.2062978.

Abstract

Circular RNAs (circRNAs) are involved in the carcinogenesis of lung cancer. Human MYC gene is highly expressed in melanoma, multiple myeloma, and nasopharyngeal carcinoma. We aimed to investigate the role of circMYC in small cell lung cancer (SCLC). The expression of cirMYC in SCLC tissues and cells were examined. Functional studies were performed to evaluate the roles of circMYC in SCLC cells. Luciferase reporter gene assay, RNA pull-down assay, and rescue experiments were performed to evaluate the regulatory relationship between circMYC and miR-145, and MiR-145 and MMP2 mRNA. We found that CirMYC was highly expressed in SCLC tissues and cells. Knockdown of circMYC could inhibit cell proliferation, migration, invasion, and induce apoptosis. CircMYC targeted miR-145 and miR-145 targeted MMP2 (Matrix Metallopeptidase 2) mRNA. Our data indicated that circMYC upregulates the expression of MMP-2 by inhibiting miR-145, which functions to promote the proliferation, migration, and invasion and inhibit the apoptosis of SCLC. These findings suggest that targeting circMYC/miR-145/MMP-2 could serve as a potential therapeutic strategy for SCLC treatment.

Keywords: MMP2; SCLC; cell proliferation; circMYC; miR-145.

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Humans
  • Lung Neoplasms* / pathology
  • Matrix Metalloproteinase 2 / genetics
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Nasopharyngeal Neoplasms*
  • RNA, Messenger
  • Small Cell Lung Carcinoma* / metabolism

Substances

  • MIRN145 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Matrix Metalloproteinase 2

Grants and funding

The author(s) reported that there is no funding associated with the work featured in this article.