MiR-132-3p inhibits proliferation, invasion and migration of colorectal cancer cells via down-regulating FOXP2 expression

Acta Biochim Pol. 2022 Jun 6;69(2):371-377. doi: 10.18388/abp.2020_5813.

Abstract

Objective: colorectal cancer (CRC) is a common cancer with high mortality. This study aimed to investigate the role of microRNA (miR)-132-3p on proliferation, invasion and migration of CRC cells.

Materials and methods: qRT-PCR and Western blot analyses were used to determine the expression of miR-132-3p and forking box (FOX) protein 2 (FOXP2) in CRC cell line CACO-2. The expression of miR-132-3p and FOX was regulated using miR inhibitor and siRNA, and the viability and migration ability of the transfected cells were assessed. Cell cycle dependent kinase (CDK) 1, cyclin D1, matrix metalloproteinase (MMP)-2 and MMP-9 were detected using Western blots. The dual luciferase reporter gene assays were used to verify the targeting of miR-132-3p to FOXP2.

Results: Compared with control cells, FOXP2 and miR-132-3p expressions were decreased or increased significantly (P<0.05), respectively in CACO-2 cells. Up-regulation of miR-132-3p effectively inhibited the proliferation, migration and invasion of CACO-2 cells, and suppressed the expression of FORX2, cyclin-dependent kinase 1 (CDK1), cyclin D1, MMP-2 and MMP-9. Luciferase reporter gene assays reveled that FOXP2 expression was negatively regulated by miR-132-3p. Knockdown of FOXP2 using siRNA significantly reduced the proliferation and migration of CACO-2 cells, down-regulated the expression FOXP2 as well as CDK1, cyclin D1, MMP-2 and MMP-9. Since FOXP2 is targeted by miR-132-3p, it is likely that miR-132-3p-mediated reduction of proliferation and migration of CACO-2 cells was achieved via reduced translation of FOXP2 mRNA.

Conclusions: miR-132-3p inhibits the proliferation, migration and invasion of CRC cells. This is likely achieved via negative regulation of the targeted FOXP2 expression. This role may be further explored for therapeutic applications in CRC.

MeSH terms

  • Caco-2 Cells
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Forkhead Transcription Factors / pharmacology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Luciferases / genetics
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • MicroRNAs* / metabolism
  • RNA, Small Interfering / pharmacology

Substances

  • FOXP2 protein, human
  • Forkhead Transcription Factors
  • MIRN132 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • Cyclin D1
  • Luciferases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9