Circadian rhythm reprogramming, type 2 diabetes and cancer progression: a meta-analysis of transcriptome data
clock genes; IGF1; USP2; metabolic syndrome; hypothalamus;
cortex; cancer
Introduction: Tumorigenesis is affected by clock genes. Changes in the expression of clock genes can increase cancer susceptibility through the effects on biological mechanisms that regulate DNA damage and repair, energy metabolism, cell growth and death in neoplastic tissues (NIRVANI et al, 2018; GERY, 2010). Objective: to analyze the association of circadian rhythm, type 2 diabetes and cancer. Methodology: The study is a meta-analysis performed on type 2 diabetes, genes related to circadian rhythm and transcriptome data associated with breast, bladder, liver, pancreas, colon and rectum cancer using the integration of gene expression profiles with biomolecular in genome scale networks in diabetes samples, the databases searched were Pubmed and TCGA. The descriptors circadian rhythm, type 2 diabetes and cancer in English were used with Boolean operators and or or. Results: several common genes deregulate in diabetes mellitus and cancer. KLF10, NTKR3, IGF1, USP2, EZH2 were both down-regulated in samples of type 2 diabetes and cancer, while ARNTL2 AND AGRP were up-regulated. It appears that changes in mRNA are contributing to phenotypic changes in type 2 diabetes, resulting in phenotypic changes associated with malignant transformation. Taking these genes to perform a survival analysis, we found only the IGF1, USP2 and ARNTL2 genes associated with patient results. While negative regulation of IGF1 and USP2 had a negative impact, positive regulation of ARNTL2 was associated with poor survival in BLCA and BRCA cancer samples. Conclusion: our data stimulate efforts in new studies to achieve experimental and clinical validation on these biomolecule