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IF 2.3 4区医学 Q3 ONCOLOGY

Current cancer drug targets Pub Date : 2025-04-03 DOI:10.2174/0115680096330893241221141235

Qiucheng Cai, Jianyong Liu, Junyang Xiao, Jianwei Chen, Lizhi Lv, Fang Yang

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引用次数: 0

摘要

目的：肝细胞癌（HCC）是一种高发恶性肿瘤，在全球癌症相关死亡原因中排名第三。尽管化疗取得了进展，但许多患者的疗效有限，最终导致顺铂耐药。因此，深入研究顺铂耐药的分子机理迫在眉睫：本研究利用GEPIA数据集分析了MED10的表达及其与HCC的关系。通过 PCR 和免疫组化对正常组织和 HCC 组织中的 MED10 表达水平进行量化。HCC 细胞增殖通过细胞活力和集落形成试验进行评估，细胞凋亡率则通过流式细胞术进行测量。为检测 PTEN 泛素化情况，在体外进行了 Western 印迹分析。此外，还使用 BALB/c 裸鼠（雄性/雌性，6 周大，18-22 克）进行异种移植肿瘤模型，以评估体内的细胞增殖情况：结果：研究结果表明，MED10通过促进PTEN泛素化，在驱动HCC顺铂耐药性方面发挥了关键作用。MED10的表达与HCC的恶性程度相关，MED10的敲除可显著降低SMMC-7721、HepG2和MHCC97-H细胞系中顺铂的IC50。MED10过表达会显著降低PTEN蛋白水平，泛素化抑制剂TAK-243可逆转这种情况，而PTEN mRNA水平则不受MED10过表达或TAK-243的影响。在体外和体内，MED10都能通过促进HCC细胞中PTEN的泛素化来增强顺铂抗性。这些结果为研究MED10表达的分子机制及其在HCC顺铂耐药中的作用提供了宝贵的见解：结论：MED10通过促进HCC细胞中PTEN泛素化增强顺铂耐药性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.

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来源期刊

Current cancer drug targets 医学-肿瘤学

CiteScore

5.40

自引率

0.00%

发文量

105

审稿时长

1 months

期刊介绍： Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.