Expression of miR-34a-5p is up-regulated in human colorectal cancer and correlates with survival and clock gene PER2 expression

PLoS One. 2019 Oct 28;14(10):e0224396. doi: 10.1371/journal.pone.0224396. eCollection 2019.

Abstract

Colorectal cancer represents a leading cause of cancer death. MicroRNAs (miRNAs) are small non-coding RNA molecules that have been extensively studied in tumours, since changes in their levels can reveal patient prognosis. Cancer progression is also influenced by the circadian system whose functioning is based on the rhythmic expression of clock genes. Therefore, we performed macroarray screening of tumour and adjacent tissues in patients undergoing surgery for colorectal carcinoma. We identified 17 miRNAs showing expression that was more than 100 times higher in tumour tissue compared to adjacent tissue. From in silico analysis, miR-34a-5p was selected as showing a computer-predicted interaction with PER2. Real-time PCR revealed a negative correlation between expression of PER2 mRNA and miR-34a in patients with more advanced cancer stage. Expression of miR-34a was up-regulated in cancer tissue compared to adjacent tissue. High miR-34a expression was associated with better survival of patients. miR-34a showed lower expression levels in male patients with lymph node involvement, and a trend towards decreased expression in male patients with distant metastases. Male patients, but not female patients, with high expression of miR-34a and who were free of distant metastases and/or lymph node involvement showed better survival. Therefore, we proposed that expression of miR-34a was regulated in a sex-dependent manner and could be considered a marker of prognosis in earlier cancer stages in male patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Period Circadian Proteins / genetics*
  • Survival Analysis
  • Up-Regulation*

Substances

  • MIRN34 microRNA, human
  • MicroRNAs
  • PER2 protein, human
  • Period Circadian Proteins

Grants and funding

This work was supported by APVV-14-0318, The Slovak Research and Development Agency, https://www.apvv.sk/?lang=en, to MZ; APVV-16-0209, The Slovak Research and Development Agency, https://www.apvv.sk/?lang=en, to IH; VEGA 1/0679/19, Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic, https://www.minedu.sk/vedecka-grantova-agentura-msvvas-sr-a-sav-vega/, to IH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.