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Exosomal miR-93 derived from hepatocellular carcinoma cell promotes the sorafenib resistance of hepatocellular
Yuanpeng Bao1, Song Xu1, Junjing Zhou1
1Department of Hepatobiliary Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
Journal of Biochemical and Molecular Toxicology
|February 20, 2024
Summary
Exosomal miR-93 promotes sorafenib resistance in hepatocellular carcinoma (HCC) by targeting PTEN. This microRNA (miRNA) can be transferred between cells, offering a potential therapeutic target for advanced HCC.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Exosomal microRNAs (miRNAs) are key regulators in cancer progression and drug resistance.
- The specific role of exosomal miRNAs in sorafenib resistance of hepatocellular carcinoma (HCC) remains largely unelucidated.
- Hepatocellular carcinoma (HCC) is a significant global health concern with limited treatment options for advanced stages.
Purpose of the Study:
- To investigate the function and mechanisms of exosomal miR-93 in sorafenib resistance in HCC.
- To determine if miR-93 is a prognostic factor in HCC patients.
- To identify the molecular targets and pathways involved in exosomal miR-93-mediated sorafenib resistance.
Main Methods:
- Utilized TCGA HCC database to analyze miR-93 levels and prognosis.
- Confirmed exosome isolation via transmission electron microscopy.
- Employed quantitative reverse transcription-polymerase chain reaction and Cy3-labeling to track exosomal miR-93 transfer.
- Assessed sorafenib resistance using CCK8, EdU, and flow cytometry assays.
- Investigated the miR-93-PTEN interaction using bioinformatics and luciferase reporter assays.
- Validated downstream pathway activation (PI3K/AKT) via Western blot.
Main Results:
- miR-93 is overexpressed in HCC and serves as a prognostic risk factor.
- miR-93 is upregulated in sorafenib-resistant HCC cells and contributes to resistance by targeting PTEN.
- Exosomes secreted by resistant cells are enriched with miR-93, promoting sorafenib resistance.
- Exosomal miR-93 reactivates the PI3K/AKT pathway by targeting PTEN, facilitating resistance spread.
Conclusions:
- Exosomal miR-93 plays a critical role in mediating sorafenib resistance in HCC.
- Targeting miR-93 presents a potential therapeutic strategy for patients with acquired sorafenib resistance.
- Understanding exosomal miRNA transfer mechanisms is crucial for developing effective HCC treatments.
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