Integrated analysis identifies low microRNA-215 expression as associated with a poor prognosis of patients with colorectal cancer through the IKß-α signaling pathway.

ABSTRACT

BACKGROUND: miRNA expression data on colorectal cancer (CRC) are constantly updated. Therefore, integrated analysis of these datasets prior to experiments is necessary in translational medicine and oncology research. Abnormal low expression of hsa-miRNA-215-5p (miR-215) is detected in several cancer types, but the role of miR-215 in CRC remains unclear. Therefore, the aim of this work was to identify the expression and role of miR-215 involved in CRC. METHODS: An integrated analysis of 4 sets of miRNA microarray data of CRC in GEO was implemented. The low expression of miR-215 in CRC was confirmed by TCGA datasets. In addition, frozen tissue and paired formalin-fixed paraffin-embedded samples were collected from 214 CRC patients who underwent CRC surgery at the Affiliated Hospital of Jiangnan University, China, and used as an independent clinical validation study. Furthermore, colon cancer cells HCT116 and SW480 transfected with miR-215 mimic/inhibitor were used to evaluate its mechanism of action and to perform experiments to confirm our results obtained from human samples. RESULTS: CRC patients with a decreased miR-215 expression in adenocarcinoma tissues had a significantly poor prognosis with lower cumulative survival as revealed by the TCGA-COAD dataset. In our 214 CRC patients cohort study this result was confirmed and it was also found that low miR-215 expression was inversely correlated with the expression of IKß-α. Downregulation of miR-215 in HCT116 and SW480 cells resulted in an upregulation of TRAF5 and TAK1 protein expression, and interfered with IKß-α protein expression. Furthermore, with the inhibition of miR-215, important Epithelial-Mesenchymal Transition (EMT) biomarker proteins were significantly upregulated in HCT116 and SW480 cells. Moreover, an inhibition was obtained using miR-215-mimic. CONCLUSIONS: Our integrated microRNA dataset approach identified miR-215 as an independent factor associated with the prognosis of CRC patients. In addition, our results demonstrated that miR-215 might be considered as a potential biomarker for poor prognosis in CRC patients and its role as a potent suppressor of IKß-α and TRAF5.