RNA-seq of human colonic cancer cell line CACO-2 transfected 48h with siRNA targeting JAK1 (HJ1D8; HJ1D2) or JAK3 (HJ3D41; HMJ3D1) at 100pM final concentration using LipofectamineRNAiMAX or treated 48h with Tofacitinib (final concentration: 1µM) or Filgotinib (final concentration: 5µM) against controls (transfection medium: Opti-MEM, transfection mixt alone: Opti-MEM + Lipof., siMock, DMSO equivalent to volume added for Filgo 5µM).
Inflammatory bowel diseases are highly debilitating conditions that require constant monitoring and life-long medication. Current treatments are focused on systemic administration of immunomodulatory drugs, but they have a broad range of undesirable side-effects. The RNA interference is a highly specific endogenous mechanism that regulates the expression of the gene at the transcript level, which can be repurposed using exogenous short interfering RNA (siRNA) in order to repress the target gene's expression. While siRNA therapeutics can offer an alternative to existing therapies, with a high specificity critical for chronically administrated drugs, evidence of their potency compared to chemical kinase inhibitors used in clinics is still lacking in alleviating an adverse inflammatory response. In this experiment, we compared the transcriptomic profile of cells transfected 48hv by siRNA targeting JAK1 and JAK3 (100 pM) to those of cells treated 48h with the most recent and promising kinase inhibitors for Janus kinases (Jakinibs), Tofacitinib (1 µM) and Filgotinib (5 µM).