MicroRNA-105 is involved in TNF-α-related tumor microenvironment enhanced colorectal cancer progression.

TNF-α is a central proinflammatory cytokine contributing to malignant tumor progression in tumor microenvironment. In this study, we found the upregulation of miR-105 in colorectal cancer was associated with aggressive phenotype, and the enhanced expression of miR-105 was required for TNF-α-induced epithelial-mesenchymal transition (EMT). The expression of miR-105 was remarkably stimulated by TNF-α in a time-dependent manner using real-time qPCR analysis. Inhibition of miR-105 remarkably weakened the aggressive effects of TNF-α through preventing the activation of NF-κB signaling and the initiation of EMT. Furthermore, miR-105 was demonstrated directly targeted on the 3'-UTRs of RAP2C, a Rap2 subfamily of small GTP-binding protein. Consistently, suppression of RAP2C stimulated the role of miR-105, which dramatically promoted the invasion and metastasis of CRC cells. Thalidomide, a TNF-α and NF-κB inhibitor, significantly weakened the metastasis and homing capacity of miR-105-overexpressed CRC cells in nude mice. Our investigation initiatively illustrated the modulatory role of miR-105 in TNF-α-induced EMT and further CRC metastasis. We also offer a better understanding of TNFα-induced metastasis and suggest an effective therapeutic strategy against CRC metastasis.