miR-1249-3p accelerates the malignancy phenotype of hepatocellular carcinoma by directly targeting HNRNPK

Mol Genet Genomic Med. 2019 Oct;7(10):e00867. doi: 10.1002/mgg3.867. Epub 2019 Aug 20.

Abstract

Background: microRNAs (miRNAs) have been implicated to play crucial roles in carcinogenesis. miR-1249-3p was reported to be abnormally expressed in multiple human cancers. However, its biological role and the associated underlying mechanisms in hepatocellular carcinoma (HCC) remain largely unknown.

Methods: miR-1249-3p expression level in HCC cell lines and normal cell line was measured by quantitative real-time PCR. Role of miR-1249-3p on HCC cell proliferation, colony formation, and invasion was examined by cell counting kit-8 assay, colony formation assay, and transwell invasion assay, respectively. Luciferase activity reporter assay and western blot were performed to validate whether heterogeneous nuclear ribonucleoprotein K (HNRNPK) was a direct target of miR-1249-3p. Effect of miR-1249-3p on overall survival of HCC patients was analyzed at KM Plotter website.

Results: We found miR-1249-3p expression level was increased, while HNRNPK expression level was decreased in HCC cell lines compared with normal cell line. Knockdown miR-1249-3p expression inhibits HCC cell proliferation, colony formation, and cell invasion through regulating HNRNPK in vitro. We also showed high miR-1249-3p expression was a predictor for poor overall survival of HCC patients.

Conclusions: These findings about miR-1249-3p/HNRNPK pair provide a novel therapeutic method for HCC patients.

Keywords: HNRNPK; miR-1249-3p; cell events; hepatocellular carcinoma.

MeSH terms

  • 3' Untranslated Regions
  • Antagomirs / metabolism
  • Base Sequence
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition
  • Heterogeneous-Nuclear Ribonucleoprotein K / antagonists & inhibitors
  • Heterogeneous-Nuclear Ribonucleoprotein K / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein K / metabolism*
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Sequence Alignment
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • Heterogeneous-Nuclear Ribonucleoprotein K
  • MIRN1249 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • HNRNPK protein, human