Long non-coding RNA H19 promotes proliferation in hepatocellular carcinoma cells via H19/miR-107/CDK6 axis

Oncol Res. 2023 Sep 15;31(6):989-1005. doi: 10.32604/or.2023.030395. eCollection 2023.


Hepatocellular carcinoma (HCC) is the leading cause of cancer death worldwide; nevertheless, current therapeutic options are limited or ineffective for many patients. Therefore, elucidation of molecular mechanisms in HCC biology could yield important insights for the intervention of novel therapies. Recently, various studies have reported dysregulation of long non-coding RNAs (lncRNAs) in the initiation and progression of HCC, including H19; however, the biological function of H19 in HCC remains unclear. Here, we show that knockdown of H19 disrupted HCC cell growth, impaired the G1-to-S phase transition, and promoted apoptosis, while overexpression of H19 yielded the opposite results. Screening for expression of cell cycle-related genes revealed a significant downregulation of CDK6 at both RNA and protein levels upon H19 suppression. Bioinformatic analysis of the H19 sequence and the 3' untranslated region (3' UTR) of CDK6 transcripts showed several binding sites for microRNA-107 (miR-107), and the dual luciferase reporter assay confirmed their direct interaction with miR-107. Consistently, blockage of miR-107 activity alleviated the growth suppression phenotypes induced by H19 downregulation, suggesting that H19 serves as a molecular sponge for miR-107 to promote CDK6 expression and cell cycle progression. Together, this study demonstrates a mechanistic function of H19 in driving the proliferation of HCC cells and suggests H19 suppression as a novel approach for HCC treatment.

Keywords: CDK6; Cyclin-dependent kinase; H19; HCC; Long-noncoding RNA; MicroRNA.

MeSH terms

  • 3' Untranslated Regions
  • Carcinoma, Hepatocellular* / genetics
  • Cell Proliferation / genetics
  • Cyclin-Dependent Kinase 6 / genetics
  • Humans
  • Liver Neoplasms* / genetics
  • MicroRNAs* / genetics
  • RNA, Long Noncoding* / genetics


  • 3' Untranslated Regions
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6
  • MicroRNAs
  • MIRN107 microRNA, human
  • RNA, Long Noncoding
  • H19 long non-coding RNA