hMSH2 与 E2F1 的表达相协调，促进上皮性卵巢癌对铂类的反应。
hMSH2 coordinated with the expression of E2F1 promotes platinum response in epithelial ovarian cancer.
机构信息
Department of Oncology, Affiliated Xingtai People Hospital of Hebei Medical University, Xingtai, China.
Department of Gynaecology, Affiliated Xingtai People Hospital of Hebei Medical, University, Xingtai, China.
出版信息
J Int Med Res. 2023 Mar;51(3):3000605231163780. doi: 10.1177/03000605231163780.
OBJECTIVE
To explore underlying mechanisms that regulate hMSH2 expression and drug susceptibility in epithelial ovarian cancer (EOC).
METHODS
Using data from the Cancer Genome Atlas (TCGA) we used bioinformatical analysis to predict transcription factors (TFs) that potentially regulate hMSH2. RT-qPCR, Western blot, and luciferase assays were undertaken using ovarian cancer cell lines to verify the identified TF. Expressions of the TF were modulated using overexpression or knockdown, and the corresponding cellular responses to cisplatin were examined.
RESULTS
The TF, E2F1, was found to regulate the hMSH2 gene. The expression level of E2F1 correlated with cisplatin susceptibility . Kaplan-Meier analysis of 77 patients with EOC showed that low E2F1 expression was associated with worse survival.
CONCLUSIONS
To our knowledge, this is the first report of E2F1 regulated MSH2 expression playing a role in drug resistance of platinum-based treatments for patients with EOC. Further work is need to confirm our results.
目的
探索调控上皮性卵巢癌（EOC）中 hMSH2 表达和药物敏感性的潜在机制。
方法
利用癌症基因组图谱（TCGA）的数据，我们采用生物信息学分析预测潜在调控 hMSH2 的转录因子（TFs）。利用卵巢癌细胞系进行 RT-qPCR、Western blot 和荧光素酶测定，以验证鉴定的 TF。通过过表达或敲低来调节 TF 的表达，并检测相应的细胞对顺铂的反应。
结果
发现 TF E2F1 可调节 hMSH2 基因。E2F1 的表达水平与顺铂敏感性相关。对 77 例 EOC 患者的 Kaplan-Meier 分析表明，E2F1 低表达与生存不良相关。
结论
据我们所知，这是首次报道 E2F1 调控 MSH2 表达在 EOC 患者铂类药物耐药中的作用。需要进一步的工作来证实我们的结果。
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