HSF1 Stimulates Glutamine Transport by Super-Enhancer-Driven lncRNA LINC00857 in Colorectal Cancer

Abstract

Super enhancers are critical for the gene transcription responsible for cell fate by interacting with transcription factors. However, the relevance of HSF1 to super enhancers in tumors remains obscure. We profiled H3K27ac enrichment by chromatin immunoprecipitation sequencing. HSF1-mediated lncRNAs were identified by lncRNA microarray. The characteristics of LINC00857 were explored by in vitro and in vivo assays. The mechanism was studied via chromatin immunoprecipitation, RNA immunoprecipitation, and HSF1/ANXA11 knockout mice. We found that super enhancers occupied multiple gene loci in colorectal cancer. We screened out an HSF1-mediated super enhancer, lncRNA-LINC00857, which exerts its characteristics in promoting cell growth via regulating glutamine metabolism. Notably, HSF1 could stimulate the super-enhancer activity of LINC00857 by the enrichment of acetyltransferase P300 to its gene loci, contributing to LINC00857 transcription. In turn, nuclear LINC00857 cooperated with HSF1 to promote ANXA11 transcription, which modulated SLC1A5/ASCT2 protein expression by binding competitively to miR-122-5p. The knockout of ANXA11 attenuated colorectal cancer formation in vivo. Collectively, we shed light on a closely cooperative machinery between HSF1 and super enhancers. HSF1 could stimulate acetyltransferase P300-mediated super-enhancer activity to facilitate LINC00857 expression, contributing to SLC1A5-mediated glutamine transport. Targeting the HSF1/LINC00857/ANXA11 axis may provide a valuable therapeutic strategy against colorectal cancer.

Pan-cancer analysis of super enhancer-induced PRR7-AS1 as a potential prognostic and immunological biomarker

“…As researches continue to advance, lncRNAs also play pivotal roles in the metabolic changes of tumors ( Lin, 2020 ). The aberrant expression of lncRNA may contribute to the dysregulation of key genes in glucose, lipid and amino acid metabolism ( Muret et al, 2019 ; Zheng et al, 2019 ); ( Shen Q. et al, 2022 ). Interestingly, metabolic reprogramming has a great impact on immunotherapy ( Lv et al, 2022 ; Yang et al, 2022 ; Zhu et al, 2022 ).…”

Pan-cancer analysis of super-enhancer-induced LINC00862 and validation as a SIRT1-promoting factor in cervical cancer and gastric cancer

“…The qPCR assays were conducted as reported previously [ 26 ]. a-Tubulin was used as the internal control.…”

“…Dual luciferase reporter assays were conducted as previously reported [ 26 ]. pMIR-REPORT-LINC00862 (WT or MT) and pMIR-REPORT-SIRT1 (WT or MT) plasmids were used.…”

Mitochondria: It is all about energy

“…The increase in the plasmatic concentration of serine and threonine is well-described in cancer ( Scalise et al, 2017c ). It seems clear that amino acids are involved in cancer metabolic rewiring, and several are essential for the initiation and progress of cancer ( Scalise et al, 2020 ; Wang et al, 2022a ; Shen et al, 2022c )…”