Evaluation of the Circadian Rhythm Component Cipc (Clock-Interacting Pacemaker) in Leukemogenesis: A Literature Review and Bioinformatics Approach.

Abstract

Circadian rhythms (CRs) are a key biological system regulating physiological processes such as metabolism, cell growth, DNA repair, and immunity, adapting to environmental changes like the light/dark cycle. Governed by internal clocks, it modulates gene expression through feedback loops involving Clock Genes (CGs), with the cycle initiated by CLOCK-BMAL1 and NPAS2-BMAL1 heterodimers. Disruptions in circadian rhythms have been linked to diseases including metabolic disorders, neurodegeneration, and cancer. CIPC (CLOCK-interacting pacemaker) has been studied as a negative regulator of the CLOCK-BMAL1 complex, focusing on its role in cancer, particularly leukemias. Public datasets and bioinformatics tools were used to examine CIPC gene expression in healthy patients and acute myeloid leukemia (AML) samples. Our analysis revealed significant overexpression of CIPC in AML compared to healthy tissues (p < 0.0001 ****). Additionally, survival analysis indicated significant differences in overall survival based on CIPC expression, with a log-rank test p-value = 0.014, suggesting that CIPC expression may affect overall patient survival. Altered CIPC expression may contribute to leukemogenesis by inhibiting circadian genes, which are often disrupted in leukemia. Furthermore, CIPC interacts with oncogenic pathways, including the MAPK/ERK pathway, which is essential for cell proliferation. Additional studies are needed to validate these findings and explore the detailed role of CIPC in cancer development.