MiR-199a/b-3p inhibits colorectal cancer cell proliferation, migration and invasion through targeting PAK4 and BCAR3

Eur J Med Res. 2022 Jul 16;27(1):121. doi: 10.1186/s40001-022-00750-8.

Abstract

Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. P21 activated kinase 4 (PAK4) and Breast cancer anti-estrogen resistance 3 (BCAR3) have been reported to be involved in numerous aspects in tumorous progression. In this study, we propose to screen multi-targeted microRNAs. (miRNAs), which simultaneously inhibit neoplastic evolution through suppressing the transcription of target genes.

Methods: MTT and Colony formation assays measured cell's viability and proliferation. Scratch wound and Transwell assays detected the ability in migration and invasion for SW116 cells. The multi-targeted microRNAs of PAK4 and BCAR3 were predicted using bioinformatics analysis and verified by conducting dual luciferase reporter assay, western blot and qRT-PCR that could detect the expression levels of miR-199a/b-3p.

Results: The knockdown of PAK4 significantly impeded proliferation and colony formation of SW1116 cells when the knockdown of BCAR3 hindered migration and invasion of SW1116 cells. MiR-199a/b-3p directly targeted the 3'-UTR of PAK4 and BCAR3, further effected proliferation, colony formation, migration, and invasion of SW1116 cells. PAK4 or BCAR3 overexpression could partially reversed inhibitory effects of miR-199a/b-3p.

Conclusions: These results provided a new multi-targeted cite for cancerous suppressant to improve the prognosis of CRC inpatients.

Keywords: BCAR3; Colorectal cancer (CRC); Mobility; PAK4; Viability; miR-199a/b-3p.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism
  • Guanine Nucleotide Exchange Factors / pharmacology
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • p21-Activated Kinases / genetics
  • p21-Activated Kinases / metabolism
  • p21-Activated Kinases / pharmacology

Substances

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing
  • BCAR3 protein, human
  • Guanine Nucleotide Exchange Factors
  • MicroRNAs
  • PAK4 protein, human
  • p21-Activated Kinases