The HMGCS2-associated hub genes as promising targets for ulcerative colitis patients

Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease of colon with unclear pathogenesis. Studies have shown that 3-hydroxy-3-methylglutaryl-CoAsynthase 2 (HMGCS2) may play an important role in inflammation, but its role in UC especially those in remission phase has not been investigated. The transcriptional profile of normal and UC patients was extracted from the Gene Expression Omnibus database (GEO), and the results revealed that HMGCS2 was significantly downregulated in both inflamed and remission samples of UC patients as compared to controls. We generated Caco-2 and HT-29 cells lacking HMGCS2 by lentivirus shRNA vectors. The analysis of RNA-seq data of the cells showed that knockdown of HMGCS2 significantly downregulated fatty acid (FA)-metabolism pathway by KEGG analysis, and HMGCS2-associated FA-metabolism-related hub genes (HubHMGCS2−FA) were retrieved. Further validation in GEO datasets showed that the HubHMGCS2−FA panel were significantly correlated with FA-metabolism pathway. The risk score modelHMGCS2−FA was then established, and its prediction effect in distinguishing UC patients in active as well as remission phase from normal controls is good (AUC:0.85-1). Therefore, HMGCS2 plays an important role in patients with UC in not only active but also remission phase and may serve as promising biomarkers and therapeutic targets in the future.