MIR133A regulates cell proliferation, migration, and apoptosis by targeting SOX9 in human colorectal cancer cells

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Santosh Lamichhane1, Ji-Su Mo2, Grinsun Sharma1

  • 1Department of Pathology, School of Medicine, Wonkwang University Iksan, Chonbuk 54538, Korea.

American Journal of Cancer Research
|August 15, 2022
PubMed

Insights

MicroRNA 133A (MIR133A) is downregulated in colorectal cancer (CRC). MIR133A targets SOX9, inhibiting CRC cell proliferation, migration, and tumor growth.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • MicroRNAs (miRNAs) play crucial roles in gene regulation and are implicated in various diseases, including cancer.
  • Colorectal cancer (CRC) is a significant global health concern with complex molecular underpinnings.
  • MIR133A has been identified as a potential tumor suppressor in several cancers, but its role in CRC requires further elucidation.

Purpose of the Study:

  • To investigate the role of microRNA 133A (MIR133A) in human colorectal cancer (CRC).
  • To identify direct target genes of MIR133A and elucidate the molecular mechanisms underlying its function in CRC.
  • To evaluate the therapeutic potential of MIR133A in CRC models.

Main Methods:

  • Bioinformatic prediction and transcriptome analysis to identify MIR133A target genes.
  • Luciferase reporter assays, quantitative RT-PCR, and Western blot to validate SOX9 as a direct MIR133A target.
  • In vitro studies using CRC cell lines with MIR133A overexpression or SOX9 knockdown.
  • In vivo studies using a xenograft mouse model.

Main Results:

  • MIR133A was found to be downregulated in human CRC tissues.
  • SRY-box transcription factor 9 (SOX9) was identified and validated as a direct target of MIR133A.
  • MIR133A overexpression suppressed CRC cell proliferation, colony formation, and migration by inhibiting SOX9 and its downstream signaling pathways (PIK3CA-AKT1-GSK3B-CTNNB1 and KRAS-BRAF-MAP2K1-MAPK1/3).
  • MIR133A overexpression also increased apoptosis and suppressed tumor growth in a xenograft model.

Conclusions:

  • MIR133A acts as a tumor suppressor in human colorectal cancer.
  • The MIR133A-SOX9 axis is a key regulatory mechanism controlling CRC cell proliferation, migration, and apoptosis.
  • MIR133A holds potential as a therapeutic agent for colorectal cancer.
Keywords:
MIR133ASOX9apoptosiscell proliferationcolorectal cancer

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