Circular RNA ITCH increases sorafenib-sensitivity in hepatocellular carcinoma via sequestering miR-20b-5p and

Related Experiment Video

Updated: Aug 19, 2025

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
06:38

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

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Xiaodong Li1, Xuedong Yin1, Heyi Bao2

  • 1Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.

Molecular and Cellular Probes
|November 28, 2022
PubMed
Abstract

Insights

This study shows circular RNA ITCH (circITCH) is downregulated in hepatocellular carcinoma (HCC) and enhances sorafenib sensitivity by regulating the miR-20b-5p/PTEN/PI3K/Akt pathway, offering a potential therapeutic target for HCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Sorafenib resistance is a major challenge in advanced hepatocellular carcinoma (HCC) treatment, leading to poor patient outcomes.
  • Understanding the molecular mechanisms underlying sorafenib resistance is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To investigate the role of circular RNA ITCH (circITCH) in regulating sorafenib resistance in HCC.
  • To elucidate the underlying molecular mechanisms by which circITCH affects sorafenib sensitivity.

Main Methods:

  • Quantitative real-time PCR to assess circITCH expression in HCC tissues and cell lines.
  • Cell transfection, MTT assays, flow cytometry, and Transwell assays to evaluate cell viability, apoptosis, and migration.
  • Bioinformatic analysis, dual luciferase reporter assays, and Western blot to identify and validate downstream targets of circITCH.

Main Results:

  • circITCH expression was significantly downregulated in HCC tissues and cells, particularly in sorafenib-resistant cells.
  • Overexpression of circITCH in resistant HCC cells enhanced sorafenib sensitivity, promoted apoptosis, and reduced migration.
  • circITCH was found to elevate PTEN expression by negatively regulating miR-20b-5p, thereby inactivating the PI3K/Akt signaling pathway.

Conclusions:

  • circITCH enhances sorafenib sensitivity in HCC by modulating the miR-20b-5p/PTEN/PI3K/Akt signaling cascade.
  • circITCH represents a promising therapeutic target for overcoming sorafenib resistance in hepatocellular carcinoma.
Keywords:
Circular ITCHHepatocellular carcinomaPTENSorafenib resistancemiR-20b-5p

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