MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA

Yihui Wang1, Qingchao Tang2, Mingqi Li1

  • 1Department of Colorectal Surgery, The Third Affiliated Hospital of Harbin Medical University, 150 Haping Road, 150081 Harbin, China.

Insights

MicroRNA-375 (miR-375) is downregulated in colorectal cancer (CRC). Restoring miR-375 inhibits CRC cell growth and tumor progression by targeting PIK3CA and the PI3K/Akt pathway.

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • Colorectal cancer (CRC) is a leading cause of cancer-related mortality.
  • MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are implicated in various cancers.
  • Aberrant miRNA expression is a hallmark of human diseases, including cancer.

Purpose of the Study:

  • To investigate the role of miR-375 in colorectal cancer.
  • To identify targets of miR-375 and elucidate its mechanism of action in CRC.

Main Methods:

  • Bioinformatic analysis to predict miR-375 targets.
  • Cell culture experiments (SW480, HCT15) to assess miR-375 effects on cell proliferation, colony formation, and cell cycle.
  • Reporter assays to confirm direct binding of miR-375 to PIK3CA 3'-UTR.
  • Western blotting to analyze protein expression (PIK3CA, p-Akt).
  • Xenograft mouse models to evaluate in vivo tumor growth inhibition.

Main Results:

  • miR-375 was significantly downregulated in human CRC cell lines and tissues.
  • PIK3CA was identified as a direct target of miR-375, with miR-375 binding to the PIK3CA 3'-UTR.
  • Overexpression of miR-375 suppressed CRC cell proliferation, colony formation, and induced cell cycle arrest.
  • miR-375 inhibited the PI3K/Akt signaling pathway.
  • Silencing PIK3CA using siRNA abrogated the inhibitory effects of miR-375 on CRC cell growth.
  • Overexpressed miR-375 repressed tumor growth in vivo.

Conclusions:

  • miR-375 acts as a tumor suppressor in colorectal cancer.
  • The tumor-suppressive function of miR-375 is mediated through the direct targeting of PIK3CA and subsequent inhibition of the PI3K/Akt signaling pathway.
  • Restoration of miR-375 may represent a potential therapeutic strategy for colorectal cancer.

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