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

PeerJ. 2022 Nov 28:10:e14285. doi: 10.7717/peerj.14285. eCollection 2022.

Abstract

Colorectal carcinoma (CRC) is the second most frequent cancer worldwide. MiR-491-3p, a tumor-suppressive microRNA (miRNA, miR), has been revealed to be abnormally expressed in CRC tissues. Meanwhile, up-regulated ubiquitous mitochondrial creatine kinase (uMtCK) contributes to CRC cell proliferation. Here we aim to explore whether aberrant miR-491-3p expression promotes CRC progression through regulating uMtCK. To this end, miR-491-3p and uMtCK levels were assessed in CRC tissues using quantitative real-time PCR (qRT-PCR). The biological roles of miR-491-3p and uMtCK in regulating CRC growth were evaluated using colony formation assay and mouse Xenograft tumour model. We found that miR-491-3p expression was decreased in CRC tissues compared with matched para-cancerous tissues, whereas uMtCK expression was increased. Functionally, miR-491-3p overexpression repressed SW480 cell growth, whereas miR-491-3p depletion accelerated SW620 cell proliferation and growth. Inversely, uMtCK positively regulated CRC cell proliferation. Mechanistically, miR-491-3p post-transcriptionally downregulated uMtCK expression by binding to 3'-UTR of uMtCK. Consequently, restoring uMtCK expression markedly eliminated the role of miR-491-3p in suppressing CRC growth. Collectively, miR-491-3p functions as a tumour suppressor gene by repressing uMtCK, and may be a potential target for CRC treatment.

Keywords: Cell proliferation; Colorectal cancer; miR-491-3p; microRNA; uMtCK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / genetics
  • Humans
  • Mice
  • MicroRNAs* / genetics

Substances

  • MicroRNAs
  • MIRN491 microRNA, human

Grants and funding

This work was supported by the Science and Technology Project of Guangzhou (No. 201904010070). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.