MED10 Increases Cisplatin Resistance by Promoting PTEN Ubiquitination of Hepatocellular Carcinoma

Objective: Hepatocellular carcinoma (HCC) is a highly prevalent malignant tumor, ranking as the third leading cause of cancer-related deaths worldwide. Despite ad-vances in chemotherapy, many patients exhibit limited therapeutic efficacy, ultimately leading to cisplatin resistance. Thus, an in-depth investigation into the molecular mecha-nisms underlying cisplatin resistance is critically needed. Materials and Methods: This study utilized the GEPIA dataset to analyze MED10 expres-sion and its association with HCC. MED10 expression levels in normal and HCC tissues were quantified via PCR and immunohistochemistry. HCC cell proliferation was assessed through cell viability and colony formation assays, while apoptosis rates were measured using flow cytometry. To examine PTEN ubiquitination, Western blot analysis was con-ducted in vitro. Additionally, xenograft tumor models were employed using BALB/c nude mice (male/female, 6 weeks old, 18-22 g) to evaluate cellular proliferation in vivo. Results: The findings reveal a pivotal role for MED10 in driving cisplatin resistance in HCC by promoting PTEN ubiquitination. MED10 expression correlated with HCC malig-nancy, and MED10 knockdown significantly reduced the IC50 of cisplatin in SMMC-7721, HepG2, and MHCC97-H cell lines. MED10 overexpression significantly decreased PTEN protein levels, which was reversed by the ubiquitination inhibitor TAK-243, while PTEN mRNA levels remained unaffected by MED10 overexpression or TAK-243. Both in vitro and in vivo, MED10 enhanced cisplatin resistance by promoting PTEN ubiquitination in HCC cells. These results offer valuable insights into the molecular mechanisms under-lying MED10 expression and its role in cisplatin resistance in HCC. Conclusions: MED10 enhances cisplatin resistance by promoting PTEN ubiquitination in HCC cells.