Transcript Μεταπτυχιακά Σεμινάρια

Μεταπτυχιακά Σεμινάρια
Σειρά Διαλέξεων 2016
Dr. Pantelis Hatzis
Prinicpal Investigator, Head of Genomics Facility
Biomedical Sciences Research Center ‘Alexander Fleming’
«The role of the long non-coding RNA WiNTRLINC1 in
intestinal homeostasis and carcinogenesis»
Τετάρτη, 26 Οκτωβρίου 2016, 17:00
κτίριο ΧΩΔ 01, αίθουσα 108, Πανεπιστημιούπολη
H διάλεξη είναι ανοιχτή στο κοινό
The canonical Wnt pathway plays a central role in stem cell maintenance, differentiation and
proliferation in the intestinal epithelium. We seek to discover novel Wnt target genes relevant to
intestinal homeostasis and carcinogenesis. We have identified a nuclear long non-coding RNA,
termed WiNTRLINC1, as a direct target of TCF4/β-catenin in colorectal cancer cells. We show that
WiNTRLINC1 acts by positively regulating the expression of its genomic neighbor ASCL2, a
transcription factor that controls intestinal stem cell fate. WiNTRLINC1 interacts with TCF4/βcatenin to mediate the juxtaposition of its promoter with the regulatory regions of ASCL2. ASCL2,
in turn, regulates WiNTRLINC1 transcriptionally, closing a feedforward regulatory loop that
controls stem cell-related gene expression. This regulatory circuitry is highly amplified in colorectal
cancer and correlates with increased metastatic potential, decreased patient survival and other
clinical features. The WiNTRLINC1-ASCL2 axis is also relevantly amplified in other cancers.