miR-4709 overexpression facilitates cancer proliferation and invasion via downregulating NR3C2 and is an unfavorable prognosis factor in colon adenocarcinoma

J Biochem Mol Toxicol. 2019 Dec;33(12):e22411. doi: 10.1002/jbt.22411. Epub 2019 Oct 17.

Abstract

To date, microRNA-4709 (miR-4709) has not been studied in colon adenocarcinoma (COAD) on the basis of experiments. In our study, we aimed to investigate the biological roles and clinical significance of miR-4709 in COAD. The expression difference between miR-4709 and NR3C2 was measured based on The Cancer Genome Atlas database and cells. Kaplan-Meier and logrank tests were applied to determine the overall survival (OS) differences according to the miR-4709 and NR3C2 expression levels. To measure whether the miR-4709 level was associated with COAD cell growth, migration, and invasion, we respectively conducted 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing, and transwell assays. A luciferase reporter assay was applied to confirm the relationship between miR-4709 and its predicted target. High expression of miR-4709 was found in COAD tissues and cells. The OS rate in the miR-4709 low expression group was significantly higher than that in the miR-4709 high expression group. Univariate and multivariate analyses exhibited that miR-4709 expression was an independent adverse prognostic factor. Exogenous miR-4709 overexpression promoted proliferation, migration, and invasion of LOVO and SW480 cells. Bioinformatics analysis and luciferase assay demonstrated that miR-4709 directly binds to the 3'-untranslated region of NR3C2. NR3C2 was lowly expressed in COAD and high expression of NR3C2 had a better prognosis compared with that in the low expression of NR3C2. Correlation analysis showed that there is a close association between the level of expression of NR3C2 and miR-4709. Accordingly, miR-4709 may function as an oncogene in COAD and provide a preclinical proof for candidate management to target new miR-4709-NR3C2 signaling for COAD therapy.

Keywords: colon adenocarcinoma; invasion; miR-4709; prognosis; proliferation.

Publication types

  • Retracted Publication

MeSH terms

  • 3' Untranslated Regions
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Antagomirs
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • Down-Regulation
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Oncogenes
  • Prognosis
  • Receptors, Mineralocorticoid / metabolism*
  • Survival Rate
  • Transfection

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • MIRN4709 microRNA, human
  • MicroRNAs
  • NR3C2 protein, human
  • Receptors, Mineralocorticoid