A Computational Analysis in a Cohort of Parkinson’s Disease Patients and Clock-Modified Colorectal Cancer Cells Reveals Common Expression Alterations in Clock-Regulated Genes

SIMPLE SUMMARY: Cancer and neurodegenerative diseases are two aging-related pathologies with differential developmental characteristics, but they share altered cellular pathways. Interestingly, dysregulations in the biological clock are reported in both diseases, though the extent and potential consequences of such disruption have not been fully elucidated. In this study, we aimed at characterizing global changes on common cellular pathways associated with Parkinson’s disease (PD) and colorectal cancer (CRC). We used gene expression data retrieved from an idiopathic PD (IPD) patient cohort and from CRC cells with unmodified versus genetically altered clocks. Our results highlight common differentially expressed genes between IPD patients and cells with disrupted clocks, suggesting a role for the circadian clock in the regulation of pathways altered in both pathologies. Interestingly, several of these genes are related to cancer hallmarks and may have an impact on the overall survival of colon cancer patients, as suggested by our analysis. ABSTRACT: Increasing evidence suggests a role for circadian dysregulation in prompting disease-related phenotypes in mammals. Cancer and neurodegenerative disorders are two aging related diseases reported to be associated with circadian disruption. In this study, we investigated a possible effect of circadian disruption in Parkinson’s disease (PD) and colorectal cancer (CRC). We used high-throughput data sets retrieved from whole blood of idiopathic PD (IPD) patients and time course data sets derived from an in vitro model of CRC including the wildtype and three core-clock knockout (KO) cell lines. Several gene expression alterations in IPD patients resembled the expression profiles in the core-clock KO cells. These include expression changes in DBP, GBA, TEF, SNCA, SERPINA1 and TGFB1. Notably, our results pointed to alterations in the core-clock network in IPD patients when compared to healthy controls and revealed variations in the expression profile of PD-associated genes (e.g., HRAS and GBA) upon disruption of the core-clock genes. Our study characterizes changes at the transcriptomic level following circadian clock disruption on common cellular pathways associated with cancer and neurodegeneration (e.g., immune system, energy metabolism and RNA processing), and it points to a significant influence on the overall survival of colon cancer patients for several genes resulting from our analysis (e.g., TUBB6, PAK6, SLC11A1).