THE INTEGRATIVE GENOMIC AND FUNCTIONAL IMMUNOLOGICAL ANALYSES OF COLORECTAL CANCER INITIATING CELLS TO MODULATE STEMNESS PROPERTIES AND THE SUSCEPTIBILIY TO IMMUNE RESPONSES [RNA-Seq]

We conducted a the transcriptomic profile of CICs or FBS cell lines, upon treatment or not with immunomodulatory or epigenetic drugs or with miRNA modulators, using the QuantSeq 3’mRNA-Seq Library Prep Kit-FWD (Lexogen). Differentially expressed genes (DEGs) were assessed in CICs and FBS cell line pairs (#1076 and 1247) upon treatment with either miRNA-15a or -196a modulators (inhibitors or mimics) or immunomodulatory or epigenetic agents (HDACi, butyrate or IFN-γ + butyrate). Numerous DEGs were detected among the comparisons of the different treatments. In CICs, N= 176, 238, 131, 168, 1155, 1237 and 1368 DEGs were significantly (p<0.05) detected following their treatment with miR-15a mimic or inhibitor, miR-196a mimic or inhibitor, butyrate, HDACi or IFN-γ + butyrate, respectively. The results corroborated the role of miRNA-15a and miRNA-196a mimics and of epigenetic drugs as beneficial treatments to improve CRC-specific immune responses through mechanisms including TGF-β signaling downmodulation, HLA and APM upregulation and negative regulation of tumorigenic pathways. CICs and FBS cell line pairs (#1076 and 1247) were treateed with either miRNA-15a or -196a modulators (inhibitors or mimics) or immunomodulatory or epigenetic agents (HDACi, butyrate or IFN-γ + butyrate).