MicroRNA‑142‑3p suppresses cell proliferation, invasion and epithelial‑to‑mesenchymal transition via RAC1‑ERK1/2

Na Xie1, Qiuping Meng2, Yixin Zhang1

  • 1Department of Pathology, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570102, P.R. China.

Insights

Decreased microRNA-142-3p (miR-142-3p) expression is linked to colorectal cancer (CRC) development. This study reveals miR-142-3p suppresses colon cancer proliferation by targeting RAC1, impacting the RAC1-ERK signaling pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Aberrant microRNA (miRNA) expression is implicated in colorectal cancer (CRC) initiation and progression.
  • The precise regulatory roles of miRNAs in colorectal tumorigenesis remain largely undefined.

Purpose of the Study:

  • To investigate the miRNA expression profile in human CRC tissues.
  • To elucidate the molecular mechanism by which miRNA-142-3p (miR-142-3p) suppresses colon cancer cell proliferation.

Main Methods:

  • miRNA expression profiling using Exiqon miRNA array.
  • Bioinformatic analysis for target gene prediction and functional analysis.
  • In vitro assays (proliferation, colony formation, Transwell) to assess miR-142-3p effects.
  • Dual-luciferase reporter assays to confirm miR-142-3p targeting of RAC1.
  • Western blotting and qRT-PCR to analyze protein and gene expression levels.

Main Results:

  • 76 miRNAs were upregulated and 102 downregulated in CRC tissues compared to adjacent non-cancerous tissues.
  • miR-142-3p was significantly downregulated in 81% of primary CRC tissues.
  • miR-142-3p mimics suppressed colon cancer cell proliferation, migration, and invasion.
  • RAC1 was identified as a direct target of miR-142-3p, and its levels were reduced by miR-142-3p mimics.
  • miR-142-3p and RAC1 inhibition decreased ERK phosphorylation, suppressing epithelial-to-mesenchymal transition.

Conclusions:

  • Aberrant miRNA expression is a key feature of colorectal cancer.
  • Downregulation of miR-142-3p may contribute to CRC tumorigenesis.
  • The miR-142-3p/RAC1/ERK signaling pathway represents a potential therapeutic target for colorectal cancer.

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