Overexpression of TICRR and PPIF confer poor prognosis in endometrial cancer identified by gene co-expression network analysis

Abstract

The incidence of endometrial cancer (EC) is intensively increasing. However, due to the complexity and heterogeneity of EC, the molecular targeted therapy is still limited. The reliable and accurate biomarkers for tumor progression are urgently demanded. After normalizing the data from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), we utilized limma and WGCNA packages to identify differentially expressed genes (DEGs). The copy number variations of candidate genes were investigated by cBioPortal. Enrichment pathways analysis was performed by ClueGO and CluePedia. The methylation status was explored by UALCAN. ROC curve and survival analysis were conducted by SPSS and Kaplan–Meier. Infiltration immune cells in microenvironment were analyzed by TISIDB. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were applied to explore potential biological pathways. Immunohistochemistry staining (IHC), cell proliferation, cell apoptosis, colony formation, migration, invasion and scratch-wound assays were performed to investigate the function of key genes in vitro . In this study, four expression profile datasets were integrated to identify candidate genes. Combined with WGCNA analysis, the top ten candidates were screened out, whose abnormal methylation patterns were extremely correlated with their expression level and they were associated with tumor grades and predicted poor survival. GSEA and GSVA demonstrated they were involved in DNA replication and cell cycle transition in EC. Gene silencing of TICRR and PPIF dramatically inhibited cell growth, migration and epithelial-mesenchymal transition (EMT) and enhanced progesterone sensitivity. Additionally, from DrugBank database, cyclosporine may be effective for PPIF targeted therapy. By integrative bioinformatics analysis and in vitro experiments, our study shed novel light on the molecular mechanisms of EC. TICRR and PPIF may promise to be potential therapeutic targets for endometrial cancer.

Characterization of DNA methylation as well as mico-RNA expression and screening of epigenetic markers in adipogenesis

“…This protein is part of the mitochondrial permeability transition pore in the inner mitochondrial membrane. Activation of this pore is thought to be related to the induction of apoptosis and necrotic cell death [ 39 ].…”

Human exposure to low dose ionizing radiation affects miR-21 and miR-625 expression levels

“…PPIF affects apoptosis and necrosis by regulating mitochondrial permeability. On the other hand, the protein encoded by this gene has a role in the progression and tumor cell migration of endometrial cancer [36]. PPIF has antagonism effects on p53 and p21 which regulate cell proliferation [37].…”

Down-regulated C4orf19 confers poor prognosis in colon adenocarcinoma identified by gene co-expression network

“…Different from the traditional molecular biology research, which is limited to the analysis of the function of a single gene or protein in malignant tumors, omics technology can systematically analyze the expression differences of a large number of genes or proteins, enabling scholars to conduct comprehensive research on tumors [6]. The Weighted Gene Correlation Network Analysis (WGCNA) technique is used to describe the gene association model between various samples to identify highly collaborative gene sets [7][8][9]. At the same time, the weighted method excludes false negative or false positive results, so that the module specificity after analysis is stronger, and the obtained hub genes have a higher correlation with tumors.…”