miR-212 as potential biomarker suppresses the proliferation of gastric cancer via targeting SOX4

J Clin Lab Anal. 2020 Dec;34(12):e23511. doi: 10.1002/jcla.23511. Epub 2020 Aug 29.

Abstract

Background: Circulating microRNAs that post-transcriptionally regulate gene expressions have been reported as promising biomarkers in cancer monitoring. This study was to identify the potential role of circulating miR-212 in gastric cancer and whether it could serve as a novel biomarker for gastric cancer.

Methods: We detected the serum levels of miR-212 in 100 health people and 110 gastric cancer patients and analyzed the relationships of the serum level of miR-212 with gastric cancer. We detected the expression of miR-212 in human gastric mucosal epithelial cell line (GES-1) and human gastric cancer cell lines (NCI-N87 and SNU-16) using qRT-PCR. Then, we detected the role of 5-aza-deoxycytidine on the epigenetic regulation of miR-212 in human gastric cancer cell lines. Furthermore, luciferase reporter assay was used to detect binding activity of miR-212 on SOX4 mRNA, and their functions on the cell proliferation and apoptosis.

Results: The expression of miR-212 was higher in health people than that in gastric cancer patients, higher in gastric mucosal epithelial cell line than that in gastric cancer cells. miR-212 can be a circulating biomarker and an independent prognostic factor of gastric cancer. Moreover, miR-212 can directly regulate the 3'UTR of SOX4 mRNA to suppress p53 and Bax, resulting gastric cancer cells proliferation inhibition and apoptosis induction.

Conclusion: Our study demonstrated that miR-212 was epigenetically downregulated in gastric cancer, and resulting low level of miR-212 can be a potential circulating biomarker and poor prognosis predicator of gastric cancer.

Keywords: 5-aza-deoxycytidine; SOX4; circulation microRNA; gastric cancer; miR-212.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / pharmacology
  • Biomarkers, Tumor / blood
  • Cell Line, Tumor
  • Decitabine / pharmacology
  • Female
  • Humans
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Prognosis
  • SOXC Transcription Factors / genetics
  • SOXC Transcription Factors / metabolism*
  • Stomach Neoplasms* / blood
  • Stomach Neoplasms* / diagnosis
  • Stomach Neoplasms* / epidemiology

Substances

  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor
  • MIRN212 microRNA, human
  • MicroRNAs
  • SOX4 protein, human
  • SOXC Transcription Factors
  • Decitabine