DKC1 promotes colorectal cancer progression and therapy resistance by dysregulating sphingolipid biosynthesis
Higher expression of Dyskerin Pseudouridine Synthase 1 (DKC1) associates with poor prognosis in colorectal cancer (CRC) patients. However, the mechanism associated with DKC1 upregulation, and its functional significance in disease pathogenesis and therapeutic resistance remains largely unexplored. Here, we performed global transcriptome sequencing outlining the molecular mechanism associated with DKC1 depletion in CRC. We show a positive feedback loop between canonical WNT signaling and DKC1, which orchestrates DKC1 expression.  Moreover, we show the role of altered sphingolipid metabolism upon DKC1 abrogation in imparting CRC oncogenicity and first-line chemotherapeutic resistance. Overall design: RNA-seq was performed on scramble (shSCRM) control and DKC1 knockdown (shDKC1-2 and shDKC1-3) SW620 cells using two distinct lentiviral shRNAs stably silencing DKC1 gene.