Gene Regulation Network of Prognostic Biomarker YAP1 in Human Cancers: An Integrated Bioinformatics Study

Abstract

Background: Yes-associated protein 1 (YAP1) is the main downstream effector of the Hippo signaling pathway, which is involved in tumorigenesis. This study aimed to comprehensively understand the prognostic performances of YAP1 expression and its potential mechanism in pan-cancers by mining databases.Methods: The YAP1 expression was evaluated by the Oncomine database and GEPIA tool. The clinical significance of YAP1 expression was analyzed by the UALCAN, GEPIA, and DriverDBv3 database. Then, the co-expressed genes with YAP1 were screened by the LinkedOmics, and annotated by the Metascape and DAVID database. Additionally, by the MitoMiner 4.0 v tool, the YAP1 co-expressed genes were screened to obtain the YAP1-associated mitochondrial genes that were further enriched by DAVID and analyzed by MCODE for the hub genes.Results: YAP1 was differentially expressed in human cancers. Higher YAP1 expression was significantly associated with poorer overall survival and disease-free survival in adrenocortical carcinoma (ACC), brain Lower Grade Glioma (LGG), and pancreatic adenocarcinoma (PAAD). The LinkedOmics analysis revealed 923 co-expressed genes with YAP1 in adrenocortical carcinoma, LGG and PAAD. The 923 genes mainly participated in mitochondrial functions including mitochondrial gene expression and mitochondrial respiratory chain complex I assembly. Of the 923 genes, 112 mitochondrial genes were identified by MitoMiner 4.0 v and significantly enriched in oxidative phosphorylation. The MCODE analysis identified three hub genes including CHCHD1, IDH3G and NDUFAF5.Conclusion: Our findings showed that the YAP1 overexpression could be a biomarker for poor prognosis in ACC, LGG and PAAD. Specifically, the YAP1 co-expression genes were mainly involved in the regulation of mitochondrial function especially in oxidative phosphorylation. Thus, our findings provided evidence of the carcinogenesis of YAP1 in human cancers and new insights into the mechanisms underlying the role of YAP1 in mitochondrial dysregulation.

Transcriptomic Context of RUNX3 Expression in Monocytes: A Cross-Sectional Analysis

“…The findings suggested repression of RUNX3 via coiled-coil-helix-coiled-coil-helix domain containing 1 ( CHCHD1) expression in circulating CD14+ cells. This negative correlation may support previous observations on mitochondrial translational machinery [ 51 ] involved in RUNX3-induced apoptosis [ 52 ]. Role of CHCHD1 for human pathologies was explicated by placing this gene in the Hippo signaling pathway.…”

“…Role of CHCHD1 for human pathologies was explicated by placing this gene in the Hippo signaling pathway. Expression of CHCHD1 was associated with yes-associated protein 1 ( YAP1 ), which is one of the crucial downstream effectors of the Hippo pathway [ 51 ]. RUNX3 showed an ability to replace the binding partner of YAP.…”

Mitochondrial Factor C20orf7 Facilitates the EMT-Mediated Cancer Cell Migration and the Proliferation of Colon Cancer In Vitro and In Vivo

“…Whether tumor cells harbor wild-type or mutated C20orf7, and the subsequent functional regulations in cancer, is intriguing. Furthermore, a study investigated the gene regulation network of Yes-associated protein 1 in cancers, which applied the Gene Ontology (GO) pathway enrichment and revealed that C20orf7 could be involved in the oxidation reduction process [ 37 ]. Further investigation of the relationship between C20orf7 and the oxidation reduction process could provide us with a better understanding of the regulation of the mitochondrial respiratory complex in oxidation regulation, and possibly increase our knowledge of whether and how this modulation may contribute to cancer formation or progression.…”

CEACAM7 expression contributes to early events of pancreatic cancer

“…From the UNC Institute’s module, RNA-seq datasets, with 178 sample sizes were chosen and scrutinized using Spearman’s correlation coefficient and characterized in volcano plots. The positive or negative correlated genes were screened by the p-value (p < 0.01) [17] .…”