Li Xing-Chen, Cheng Yuan, Yang Xiao, Zhou Jing-Yi, Dong Yang-Yang, Shen Bo-Qiang, Wang Jia-Qi, Zhao Li-Jun, Wang Zhi-Qi, Li Xiao-Ping, Wang Jian-Liu
Department of Obstetrics and Gynecology, Peking University People's Hospital Beijing, China.
Beijing Key Laboratory of Female Pelvic Floor Disorders Diseases Beijing, China.
Am J Transl Res. 2020 Jul 15;12(7):3926-3939. eCollection 2020.
Transient Receptor Potential Melastatin 4 (TRPM4) is a nonselective channel conducting monovalent ions and indirectly regulates intracellular Ca. Aberrant expression has been reported in a number of cancers. However, the biological function of TRPM4 in endometrial carcinoma (EC) is still unknown. We find that decreased TRPM4 expression is significantly correlated with a poor prognosis, overall survival (OS, P<0.001) and recurrence-free survival (P=0.002) through The Cancer Genome Atlas (TCGA) datasets in mRNA level. Multivariate Cox regression analysis suggests that TRPM4 is an independent prognostic factor for OS in EC patients. assays show that TRPM4-deletion results in significant promotion of proliferation and migration in EC cells. We then conducted a gene set enrichment analysis (GSEA) and according to the results, the expression of TRPM4 is modulated by estrogen, which is inhibited by ER antagonist. Furthermore, the silencing of TRPM4 causes a decreased p53 and hyper-activation of EMT, PI3K/AKT/mTOR signaling pathway in EC, as demonstrated . Overall, these results indicate that TRPM4 is clinically useful in predicting EC prognosis and represent a potential candidate as a new therapeutic target.
瞬时受体电位褪黑素4（TRPM4）是一种传导单价离子的非选择性通道，间接调节细胞内钙。已有报道称其在多种癌症中表达异常。然而，TRPM4在子宫内膜癌（EC）中的生物学功能仍不清楚。我们发现，通过癌症基因组图谱（TCGA）数据集在mRNA水平上，TRPM4表达降低与预后不良、总生存期（OS，P<0.001）和无复发生存期（P=0.002）显著相关。多变量Cox回归分析表明，TRPM4是EC患者OS的独立预后因素。实验表明，TRPM4缺失导致EC细胞增殖和迁移显著增加。然后我们进行了基因集富集分析（GSEA），结果显示，TRPM4的表达受雌激素调节，而雌激素拮抗剂可抑制这种调节。此外，如所示，TRPM4沉默导致EC中p53降低以及EMT、PI3K/AKT/mTOR信号通路过度激活。总体而言，这些结果表明TRPM4在预测EC预后方面具有临床应用价值，并且是一种有潜力的新型治疗靶点候选物。
