Downregulated miRNA-491-3p accelerates colorectal cancer growth by increasing uMtCK expression

Xingkui Tang1, Yukun Lin2, Jialin He1

  • 1Department of General Surgery, Panyu District Central Hospital, Guangzhou, China.

Peerj
|December 15, 2022
PubMed

Insights

MicroRNA-491-3p (miR-491-3p) acts as a tumor suppressor in colorectal cancer (CRC) by downregulating ubiquitous mitochondrial creatine kinase (uMtCK). Lower miR-491-3p and higher uMtCK levels promote CRC progression, suggesting therapeutic potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Colorectal carcinoma (CRC) is a major global health concern.
  • Tumor-suppressive microRNA-491-3p (miR-491-3p) is dysregulated in CRC.
  • Increased ubiquitous mitochondrial creatine kinase (uMtCK) expression promotes CRC cell proliferation.

Purpose of the Study:

  • To investigate the role of aberrant miR-491-3p expression in colorectal cancer progression.
  • To determine if miR-491-3p regulates uMtCK in CRC.
  • To explore the potential of miR-491-3p as a therapeutic target for CRC.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) to assess miR-491-3p and uMtCK levels in CRC tissues.
  • Colony formation assays and mouse xenograft models to evaluate the biological roles of miR-491-3p and uMtCK.
  • Luciferase reporter assays to confirm the binding of miR-491-3p to the 3'-UTR of uMtCK.

Main Results:

  • miR-491-3p expression was significantly decreased in CRC tissues, while uMtCK expression was increased.
  • Overexpression of miR-491-3p inhibited CRC cell growth, whereas its depletion promoted proliferation.
  • uMtCK positively regulated CRC cell proliferation, and miR-491-3p post-transcriptionally downregulated uMtCK.
  • Restoring uMtCK expression abolished the tumor-suppressive effects of miR-491-3p.

Conclusions:

  • miR-491-3p functions as a tumor suppressor in colorectal cancer by repressing uMtCK expression.
  • The miR-491-3p/uMtCK axis represents a potential therapeutic strategy for CRC treatment.

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