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Long non‑coding RNA H19 is involved in sorafenib resistance in hepatocellular carcinoma by upregulating miR‑675

Yongzi Xu1, Yanhui Liu2, Zhenrong Li3

  • 1Department of General Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu 210009, P.R. China.

Oncology Reports
|July 7, 2020
PubMed

Insights

Long non-coding RNA H19 promotes sorafenib resistance in hepatocellular carcinoma (HCC) by upregulating miR-675 and enhancing epithelial-mesenchymal transition (EMT). Targeting H19 may offer new therapeutic strategies for drug-resistant liver cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Sorafenib is a first-line treatment for advanced hepatocellular carcinoma (HCC).
  • Drug resistance in HCC limits treatment efficacy, necessitating novel therapeutic strategies.
  • Long non-coding RNAs (lncRNAs) are implicated in tumor drug resistance, but the role of lncRNA H19 in HCC sorafenib resistance is underexplored.

Purpose of the Study:

  • To investigate the role of lncRNA H19 in sorafenib resistance in HCC.
  • To elucidate the underlying molecular mechanisms involving H19, miR-675, and epithelial-mesenchymal transition (EMT).

Main Methods:

  • Cell Counting Kit-8 (CCK-8) assay for cell viability.
  • Reverse transcription quantitative polymerase chain reaction (RT-qPCR) for gene expression analysis.
  • EdU staining, immunofluorescence staining, and western blot analysis to assess cellular proliferation, EMT markers, and protein expression.

Main Results:

  • H19 expression was negatively correlated with sorafenib sensitivity in HCC cells.
  • Knockdown of H19 increased sorafenib sensitivity by suppressing EMT.
  • H19 upregulated miR-675; miR-675 inhibition decreased cell viability, while overexpression increased it in sorafenib-treated HCC cells.
  • H19's effect on sorafenib sensitivity was dependent on miR-675 levels.

Conclusions:

  • lncRNA H19 promotes sorafenib resistance in HCC.
  • The H19/miR-675 axis plays a crucial role in regulating sorafenib sensitivity and EMT in HCC.
  • Targeting H19 presents a potential therapeutic avenue for overcoming sorafenib resistance in liver cancer patients.
Keywords:
long non‑coding RNAH19miR‑675chemosensitivityepithelial‑mesenchymal transitionhepatocellular carcinoma

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