State-Dependent Decoupling of a CREM-Centric cAMP-Responsive Regulon and Survival in Hepatocellular Carcinoma

Background

The cAMP-responsive element modulator (CREM) has emerged as a cAMP-responsive transcriptional node associated with dysfunctional lymphocyte states in chronic hepatic infection and some immunosuppressive tumor microenvironments, but its regulatory output and isoform usage by specific cell-types remain insufficiently defined in hepatocellular carcinoma (HCC). Because CREM produces activating isoforms and repressive inducible cAMP early repressor (ICER) isoforms through alternative promoter usage, bulk or single-cell CREM mRNA abundance may not faithfully describe the net direction of downstream CRE-dependent transcriptional programs.