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A Positive Regulatory Loop between a Wnt-Regulated Non-coding RNA and ASCL2 Controls Intestinal Stem Cell Fate

dc.creatorGiakountis A., Moulos P., Zarkou V., Oikonomou C., Harokopos V., Hatzigeorgiou A.G., Reczko M., Hatzis P.en
dc.date.accessioned2023-01-31T07:41:34Z
dc.date.available2023-01-31T07:41:34Z
dc.date.issued2016
dc.identifier10.1016/j.celrep.2016.05.038
dc.identifier.issn22111247
dc.identifier.urihttp://hdl.handle.net/11615/72271
dc.description.abstractThe canonical Wnt pathway plays a central role in stem cell maintenance, differentiation, and proliferation in the intestinal epithelium. Constitutive, aberrant activity of the TCF4/β-catenin transcriptional complex is the primary transforming factor in colorectal cancer. We identify a nuclear long non-coding RNA, termed WiNTRLINC1, as a direct target of TCF4/β-catenin in colorectal cancer cells. WiNTRLINC1 positively regulates the expression of its genomic neighbor ASCL2, a transcription factor that controls intestinal stem cell fate. WiNTRLINC1 interacts with TCF4/β-catenin 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 and decreased patient survival. Our results uncover the interplay between non-coding RNA-mediated regulation and Wnt signaling and point to the diagnostic and therapeutic potential of WiNTRLINC1. © 2016 The Author(s).en
dc.language.isoenen
dc.sourceCell Reportsen
dc.source.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84975138424&doi=10.1016%2fj.celrep.2016.05.038&partnerID=40&md5=c4e8ed6d1296382c4ba5f2939d2980b8
dc.subjectbeta cateninen
dc.subjectlong untranslated RNAen
dc.subjectmembrane proteinen
dc.subjectprotein ASCL2en
dc.subjectRNA polymerase IIen
dc.subjectunclassified drugen
dc.subjectWNT regulated lincRNA 1en
dc.subjectASCL2 protein, humanen
dc.subjectbasic helix loop helix transcription factoren
dc.subjectlong non-coding RNA WiNTRLINC1, humanen
dc.subjectlong untranslated RNAen
dc.subjectacetylationen
dc.subjectArticleen
dc.subjectchromatin immunoprecipitationen
dc.subjectcontrolled studyen
dc.subjectgene amplificationen
dc.subjectgene expression profilingen
dc.subjectgene expression regulationen
dc.subjectgenetic transcriptionen
dc.subjecthigh throughput sequencingen
dc.subjecthumanen
dc.subjecthuman cellen
dc.subjectintestinal stem cellen
dc.subjectmolecular cloningen
dc.subjectpolyadenylationen
dc.subjectpriority journalen
dc.subjectpromoter regionen
dc.subjectprotein conformationen
dc.subjectprotein RNA bindingen
dc.subjecttranscription initiation siteen
dc.subjecttranscription regulationen
dc.subjectWnt signaling pathwayen
dc.subjectcell lineageen
dc.subjectcolorectal tumoren
dc.subjectgeneticsen
dc.subjectintestineen
dc.subjectmetabolismen
dc.subjectpathologyen
dc.subjectstem cellen
dc.subjecttumor cell lineen
dc.subjectWnt signalingen
dc.subjectBasic Helix-Loop-Helix Transcription Factorsen
dc.subjectCell Line, Tumoren
dc.subjectCell Lineageen
dc.subjectColorectal Neoplasmsen
dc.subjectGene Expression Regulation, Neoplasticen
dc.subjectHumansen
dc.subjectIntestinesen
dc.subjectRNA, Long Noncodingen
dc.subjectStem Cellsen
dc.subjectWnt Signaling Pathwayen
dc.subjectElsevier B.V.en
dc.titleA Positive Regulatory Loop between a Wnt-Regulated Non-coding RNA and ASCL2 Controls Intestinal Stem Cell Fateen
dc.typejournalArticleen


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