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

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.

KEYWORDS:

• BMAL1
• CLOCK
• circadian rhythm
• colorectal cancer

Authors contributions

NS, JQ and SKR analyzed and interpreted the GEO data, drafted the manuscript and prepared figures and tables, AS and AA contributed significantly in analyzing TCGA data and drafting manuscript, MFAM aided in conception, design and implementation of the study and revised the paper manuscript. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The current study is funded by Higher Education Commission (HEC), Pakistan under the Project ID: 2989.