Integrated bioinformatics and experiments reveal the roles and driving forces for HSF1 in colorectal cancer

Abstract

ABSTRACT Heat shock factor 1 (HSF1) has watershed significance in different tumors. However, the roles and driving forces for HSF1 in colorectal cancer (CRC) are poorly understood. Our study integrally analyzed the roles and driving forces for HSF1 in CRC by bioinformatics and experiments. The expression and prognostic characteristics of HSF1 were analyzed via UALCAN, GEPIA2, TISIDB, Prognoscan and HPA databases. Then, we analyzed the correlation between HSF1 expression and immune features via TIMER2 database. Subsequently, we explored the driving forces for HSF1 abnormal expression in CRC by bioinformatics and experiments. Our results showed that HSF1 was overexpressed and correlated with poor prognosis in CRC. And the expression of HSF1 was significantly correlated with multiple immune cell infiltration and was negatively correlated with immunomodulators such as programmed cell death 1 ligand 1(PD-L1). Along with many driver genes in particular TP53, super-enhancer, miRNA and DNA methylation were all responsible for HSF1 overexpression in CRC. Moreover, we demonstrated that β-catenin could promote the translation process of HSF1 mRNA by interacting with HuR, which could directly bind to the coding sequence (CDS) region of HSF1 mRNA. Collectively, HSF1 may be useful as a diagnostic and prognostic biomarker for CRC. HSF1 was closely correlated with immune features. Genetic and epigenetic alterations contributed to HSF1 overexpression in CRC. More importantly, we demonstrated that HSF1 may be regulated at the level of mRNA translation by β-catenin-induced HuR activity.