Evaluation of key regulatory elements in cholesterol homeostasis and their clinical relevance in colorectal cancer

Abstract

Metabolic reprogramming is now considered one of the hallmarks of cancer. Rewiring of lipid metabolism has been reported to be associated with carcinogenesis. Cholesterol, an important class of lipids, is a vital for maintaining normal cell physiology. Accumulation of cholesterol in tumor cells is now a well established fact. Numerous in vitro studies suggested the role of various cholesterol regulators in CRC. However, the clinical relevance of these regulators is not completely understood. In the present study, we evaluated the diagnostic and prognostic value of the cholesterol homeostasis modulators by analyzing their mRNA and miRNA expression in the CRC patient samples. The expression of LDLR, SREBP2 and LXRs was also analyzed by Western Blotting. The increased tumoral expression of LDLR and SREBP2 and decreased and#61692; Note: Research Scholars are requested to please fill this metadata form in MS-Word format and save it in PDF format in their CD (thesis). Scanned copy of the same is not allowed. (Signature of Research Scholar) tumoral expression of LXRs in in early stage suggested the importance of cholesterol uptake and efflux as initial events in cancer. Cholesterol homeostasis proteins also correlated with other known tumor biomarkers. SREBF2, NR1H3 and NR1H2 exhibited the potential to discriminate the tumor and normal tissue specimens. miR-144-3p and miR-663b exhibited the potential to discriminate the early and late stage patients. Survival analysis revealed that HMGCR, NR1H3, NR1H2 could predict the patient outcome in various clinical subgroups of CRC patients but failed to be used as independent prognostic markers. However, their combinatorial gene expression had the potential to be used as the prognostic markers. Thus, the present study suggested that the key modulators of cholesterol homeostasis are deregulated in CRC patients. As these regulators are deregulated in early stages, these findings may provide novel leads in the development of biomarkers and therapeutic regimens that can detect and target CRC