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Decreased expression of TRPM4 is associated with unfavorable prognosis and aggressive progression of endometrial carcinoma.

ABSTRACT: Transient Receptor Potential Melastatin 4 (TRPM4) is a nonselective channel conducting monovalent ions and indirectly regulates intracellular Ca²⁺. 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. In vitro 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 in vitro. Overall, these results indicate that TRPM4 is clinically useful in predicting EC prognosis and represent a potential candidate as a new therapeutic target.

SUBMITTER: Li XC

PROVIDER: S-EPMC7407693 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Decreased expression of TRPM4 is associated with unfavorable prognosis and aggressive progression of endometrial carcinoma.

Li Xing-Chen XC Cheng Yuan Y Yang Xiao X Zhou Jing-Yi JY Dong Yang-Yang YY Shen Bo-Qiang BQ Wang Jia-Qi JQ Zhao Li-Jun LJ Wang Zhi-Qi ZQ Li Xiao-Ping XP Wang Jian-Liu JL

American journal of translational research 20200715 7

Transient Receptor Potential Melastatin 4 (TRPM4) is a nonselective channel conducting monovalent ions and indirectly regulates intracellular Ca<sup>2+</sup>. 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 At ...[more]

PMID: 32774746

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Decreased expression of TRPM4 is associated with unfavorable prognosis and aggressive progression of endometrial carcinoma.

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Decreased expression of TRPM4 is associated with unfavorable prognosis and aggressive progression of endometrial carcinoma.

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