miR-4323 targets hepatoma-derived growth factor (HDGF) to suppress colorectal cancer cell proliferation

Pathol Res Pract. 2021 Sep:225:153544. doi: 10.1016/j.prp.2021.153544. Epub 2021 Jul 9.

Abstract

MicroRNAs (miRNAs) are regulators of cancer progression via directly binding to the 3' untranslated region (3'UTR) of target genes to control the activity of signaling network. Recent studies have revealed the function of several miRNAs in colorectal cancer, however, there are still numerous miRNAs which have not been studied yet. Herein, we showed that miR-4323 was a downregulated miRNA according to previous microarray data. The downregulation of miR-4323 was further confirmed in colorectal tumors via RT-qPCR. miR-4323 overexpression decreased cell proliferation rate via induction of cell apoptosis in colorectal cancer cells. Mechanistically, miR-4323 decreased β-catenin and its downstream genes including c-Myc and MMP9 in colorectal cancer cells, indicating the inactivation of Wnt signaling. HDGF, an anti-apoptotic protein, was predicted by several software as a potential target of miR-4323. HDGF was experimentally verified as a target gene of miR-4323 using dual luciferase reporter assay. Ectopic expression of HDGF attenuated the effect of miR-4323 on cell proliferation and apoptosis in cells. Altogether, the data demonstrate a critical role of miR-4323 in the regulation of colorectal cancer.

Keywords: Cell proliferation; Colorectal cancer; HDGF; MicroR-4323.

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism

Substances

  • Intercellular Signaling Peptides and Proteins
  • MIRN-4323 microRNA, human
  • MicroRNAs
  • hepatoma-derived growth factor