Energy stress-induced circEPB41(2) regulates lipogenesis through histone modifications [RNA-seq]
The list of circular RNAs (circRNAs) involved in tumor metabolic reprogramming is rapidly increasing, but whether circRNAs have a role in linking epigenetic modification with lipid metabolism remains elusive. Here, we demonstrate that the circRNA circEPB41(2), which expression is driven by HNRNPA1 in response to glucose deprivation, is important for de novo lipogenesis. Moreover, we uncovered a genome-wide decrease in specific histone acetylation after circEPB41(2) depletion. These changes are associated with altered gene expression and observed cellular phenotypes, suggesting their functional significance. Mechanistically, we showed that circEPB41(2) regulates histone acetylation in part by modulating the stability and polyadenylation of SIRT6 through binding and maintaining the demethylase activity of FTO. Accordingly, circEPB41(2) silencing inhibited cellular lipid accumulation, suppressed cell proliferation, and inhibited cancer xenograft growth. Thus, circEPB41(2) may consider a target for cancer treatment. Overall design: Comparative gene expression profiling analysis of RNA-seq data for control  and circEPB41(2) shRNA-knockdown cells (sh#1, sh#2).