Dysregulation of core circadian genes, BMAL1 and CLOCK, in colorectal cancer

Abstract

ABSTRACT Circadian clock associates with several cellular processes, which are important in molecular carcinogenesis. Accordingly, aberrant expression of BMAL1 and CLOCK (core components of circadian pathway) has been identified in cancers. In present study, transcript expression of BMAL1 and CLOCK was assessed, and proteins interactions were mapped, in colorectal cancer (CRC). Low BMAL1 gene expression was observed in tumors as compared to normal tissue samples from GSE39582, GSE21510 and TCGA publicly available datasets for CRC. BMAL1 and CLOCK were suppressed in APC low (WNT activated) and MYC high tumors. Moreover, BMAL1 was slightly upregulated in TGFβ-activated and BRAF-mutated tumors, whereas CLOCK was overexpressed in KRAS-mutated tumors. Protein interaction network of the core circadian molecules identified important CRC-related proteins physically associating with BMAL1 and CLOCK. Therefore, expressional correlation of circadian drivers with frequently altered pathways in CRC as well as interactions of BMAL1 and CLOCK with physiologically functional proteins highlight their importance in CRC while paving way for in depth study of circadian pathway in oncogenesis.