MicroRNA miR-124-3p suppresses proliferation and epithelial-mesenchymal transition of hepatocellular carcinoma via ARRDC1 (arrestin domain containing 1)

Bioengineered. 2022 Apr;13(4):8255-8265. doi: 10.1080/21655979.2022.2051686.

Abstract

Hepatocellular carcinoma (HCC) is responsible for high morbidity and mortality worldwide. Increasing evidence suggests that microRNAs intensively participate in HCC development and progression. In the current study, we aimed to explore the impact of miR-124-3p in the proliferation and epithelial-mesenchymal transition (EMT) of HCC. The RT-qPCR assay was employed to determine miR-124-3p expression in human HCC specimens and cell lines. Luciferase assay was used to validate the miR-124-3p target gene. Western Blot and RT-qPCR were performed to study the effects of miR-124-3p modulation on ARRDC1 (Arrestin Domain Containing 1) mRNA and protein expressions. MTT assay, wound healing assay, EdU assay, and Transwell assay were utilized to verify the impact of miR-144-3p modulation on HCC proliferation and EMT via ARRDC1. We found that MiR-124-3p expression downregulates in HCC. Overexpression of miR-124-3p reduced the HCC cell proliferation and EMT. Meanwhile, we determined that the expression of ARRDC1 is increased in HCC, and miR-124-3p directly binds the 3'UTR of ARRDC1 and inhibits its expression at mRNA and protein level, suggesting that miR-124-3p was capable of negatively modulating ARRDC1. Besides, cotransfection of ARRDC1-overexpression plasmid and miR-124-3p mimics increased the cell proliferation and EMT as compared to miR-124-3p mimics. Our study concluded that miR-124-3p directly binds the 3'UTR of ARRDC1 and exerts anti-tumorous effects by inhibiting the HCC proliferation and EMT. Therefore, miR-124-3p/ARRDC1 axis may serve as a novel therapeutic target to inhibit HCC growth and metastasis.

Keywords: epithelial–mesenchymal transition; hepatocellular carcinoma; microRNA; proliferation.

MeSH terms

  • 3' Untranslated Regions
  • Arrestins* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Humans
  • Liver Neoplasms* / metabolism
  • MicroRNAs* / metabolism

Substances

  • 3' Untranslated Regions
  • ARRDC1 protein, human
  • Arrestins
  • MIRN124 microRNA, human
  • MicroRNAs

Grants and funding

The author(s) reported that there is no funding associated with the work featured in this article.