Simple SummaryColorectal cancer (CRC) is one of the main tumor pathologies in our society considering its incidence and mortality. Various authors have linked the development of CRC with overweight and obesity. However, no molecular markers have been defined to connect both pathologies and that can be assessed in serum for diagnostic and/or prognostic purposes. The main objective of this work is to analyze and correlate the expression levels of four miRNAs previously associated with cancer and/or obesity in patients affected by CRC, as well as in a control group without cancer, considering the body mass index (BMI) of subjects. The main novelty of this study consists in the variety of samples investigated: adipose tissues, omental and subcutaneous; serum; and tumor and non-tumor tissues in the case of CRC patients. Results from this work allow us to conclude about the utility mainly of hsa-miR-143-3p and hsa-miR-181a-5p in the clinical management of CRC.AbstractThis work aims to investigate the expression levels of four preselected miRNAs previously linked to cancer and/or obesity, with the purpose of finding potential biomarkers in the clinical management of CRC developed by patients showing different BMI values. We analyzed samples from a total of 65 subjects: 43 affected by CRC and 22 without cancer. Serum and both subcutaneous and omental adipose tissues (SAT and OAT) were investigated, as well as tumor and non-tumor colorectal tissues in the case of the CRC patients. The relative expression (2−∆∆Ct) levels of 4 miRNAs (hsa-miR-181a-5p, hsa-miR-143-3p, has-miR-132-3p and hsa-miR-23a-3p) were measured by RT-qPCR. Serum, SAT and OAT expression levels of these miRNAs showed significant differences between subjects with and without CRC, especially in the group of overweight/obese subjects. In CRC, serum levels of hsa-miR-143-3p clearly correlated with their levels in both SAT and OAT, independently of the BMI group. Moreover, hsa-miR-181a-5p could be considered as a biomarker in CRC patients with BMI ≥ 25 Kg/m2and emerges as a tumor location marker. We conclude that both adiposity and CRC induce changes in the expression of the miRNAs investigated, and hsa-miR-143-3p and hsa-miR-181a-5p expression analysis could be useful in the clinical management of CRC.