Related Experiment Video

Updated: Sep 6, 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

9.0K

miR-15a and miR-20b sensitize hepatocellular carcinoma cells to sorafenib through repressing CDC37L1 and consequent

Li Li1, Shijun Yu1, Jingde Chen1

  • 1Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.

Cell Death Discovery
|June 27, 2022
PubMed

Insights

MicroRNAs miR-15a and miR-20b enhance sorafenib sensitivity in hepatocellular carcinoma (HCC) by targeting CDC37L1. High CDC37L1 and PPIA expression predicts poor prognosis in HCC patients receiving sorafenib.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Sorafenib is a targeted therapy for advanced hepatocellular carcinoma (HCC).
  • Intrinsic resistance to sorafenib limits its effectiveness in HCC treatment.
  • Identifying mechanisms of sorafenib resistance is crucial for improving patient outcomes.

Purpose of the Study:

  • To identify genes influencing sorafenib resistance in HCC using CRISPR/Cas9 screening.
  • To elucidate the molecular mechanisms underlying sorafenib resistance and sensitivity.
  • To explore potential therapeutic targets and prognostic biomarkers for HCC treated with sorafenib.

Main Methods:

  • CRISPR/Cas9 genome-scale screening to identify genes affecting sorafenib resistance.
  • Functional assays including cell viability, colony formation, and flow cytometry to assess miRNA effects.
  • In vitro and in vivo experiments to evaluate the role of CDC37L1 in sorafenib resistance.
  • Immunohistochemical staining of HCC tissue microarrays to analyze protein expression and patient prognosis.

Main Results:

  • Deficiency of miR-15a and miR-20b was linked to sorafenib resistance in HCC cells.
  • Exogenous expression of miR-15a and miR-20b increased sorafenib sensitivity.
  • CDC37L1 was identified as a common target of miR-15a and miR-20b, and its deficiency enhanced sorafenib sensitivity.
  • CDC37L1 promotes sorafenib resistance by increasing PPIA expression via HSP90.
  • High CDC37L1 and PPIA expression correlated with worse prognosis in HCC patients treated with sorafenib.

Conclusions:

  • miR-15a and miR-20b play critical roles in modulating sorafenib response in HCC.
  • CDC37L1 and PPIA are key mediators of sorafenib resistance in HCC.
  • These molecules represent potential therapeutic targets and prognostic biomarkers for HCC patients undergoing sorafenib treatment.

More Related Videos

An In Vitro Protocol for Evaluating MicroRNA Levels, Functions, and Associated Target Genes in Tumor Cells09:45

An In Vitro Protocol for Evaluating MicroRNA Levels, Functions, and Associated Target Genes in Tumor Cells

Published on: May 21, 2019

8.5K
In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines08:50

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines

Published on: April 18, 2025

530

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.8K