ROLE OF EXOSOMAL miRNAs IN METASTATIC POST-TRANSPLANT COLORECTAL CARCINOMA UNDER RAPAMYCIN AND CYCLOSPORINE (miRNA-4)

Immunosuppression plays a crucial role in the development of cancer which remains a major cause of mortality in kidney transplant recipients. Cancer Exosomes (Exos) are extracellular vesicles described as modulators of tumor invasion and metastasis. This paper describes the effect of RAPA and CsA, two immunosuppressive drugs with different oncogenic proprieties, in Exos of colorectal cancer (CRC) cell lines. RAPA induces an increased Exos production and an overexpression of miR-6127, miR-6746-5p, and miR-6787-5p in Exos from a metastatic cell line. These miRNAs produce a significant down-regulation of epigenetic genes involved in cell cycle, chromatin and DNA regulation pre-metastatic niche. Our results describe a potential mechanism by RAPA in modulating pre-metastatic niche in post-transplant metastatic CRC through these exosomal miRNAs. HCT166 and SW480 cell lines were treated with Rapamycin and cyclosporine using two replicates.Untreated cell lines were also included.