Heat Shock Protein B7 Inhibits the Progression of Endometrial Carcinoma by Inhibiting PI3K/AKT/mTOR Pathway.

Abstract

To investigate the role and mechanism of action of Heat shock protein B7 (HSPB7) in endometrial carcinoma (EC). GEPIA (Gene Expression Profiling Interactive Analysis) was used to analyze the expression and prognostic value of HSPB7 in TCGA data. HSPB7 mRNA and protein expression levels were detected by qRT-PCR and Western blot, respectively. EC cell proliferation, apoptosis, migration, and invasion were determined by colony formation, EdU, flow cytometry, and transwell assays. Mitochondrial membrane potential was determined using JC-1 probe. In addition, apoptosis-related and metastasis-related proteins were quantitatively evaluated. A gene set enrichment analysis of the signaling pathways by which HSPB7 influences EC was performed and the levels of enriched pathway-related proteins were evaluated. We first proved that HSPB7 was downregulated in EC tissues and HSPB7 levels were positively related to survival rates. In functional assays, HSPB7 overexpression suppressed the proliferation, migration, and invasion of EC cells and conversely promoted apoptosis. Moreover, HSPB7 overexpression decreased the mitochondrial membrane potential of EC cells significantly. Bioinformatics analyses revealed that the PI3K/AKT/mTOR pathway was significantly enriched in EC. HSPB7 inhibited the phosphorylation of the PI3K/AKT/mTOR pathway to reduce proliferation, migration and invasion, and increased apoptosis in EC cells. HSPB7 was downregulated in EC and influenced EC cell proliferation, invasion, migration, and apoptosis via the PI3K/AKT/mTOR signaling pathway. These findings provide a novel perspective for the development of EC treatment strategies.