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Staufen1 Represses the FOXA1-Regulated Transcriptome by Destabilizing FOXA1 mRNA in Colorectal Cancer Cells.
Pasterczyk, Katherine R; Li, Xiao Ling; Singh, Ragini; Zibitt, Meira S; Hartford, Corrine Corrina R; Pongor, Lorinc; Jenkins, Lisa M; Hu, Yue; Zhao, Patrick X; Muys, Bruna R; Kumar, Suresh; Roper, Nitin; Aladjem, Mirit I; Pommier, Yves; Grammatikakis, Ioannis; Lal, Ashish.
Afiliación
  • Pasterczyk KR; Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Li XL; Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Singh R; Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Zibitt MS; Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Hartford CCR; Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Pongor L; DNA Replication Group, Developmental Therapeutics Branch, CCR, NCI, NIH, Bethesda, Maryland, USA.
  • Jenkins LM; Mass Spectrometry Section, Laboratory of Cell Biology, CCR, NCI, NIH, Bethesda, Maryland, USA.
  • Hu Y; Omics Bioinformatic Facility, Genetics Branch, CCR, NCI, NIH, Bethesda, Maryland, USA.
  • Zhao PX; Omics Bioinformatic Facility, Genetics Branch, CCR, NCI, NIH, Bethesda, Maryland, USA.
  • Muys BR; Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Kumar S; Molecular Pharmacology Group, Developmental Therapeutics Branch, CCR, NCI, NIH, Bethesda, Maryland, USA.
  • Roper N; Molecular Pharmacology Group, Developmental Therapeutics Branch, CCR, NCI, NIH, Bethesda, Maryland, USA.
  • Aladjem MI; DNA Replication Group, Developmental Therapeutics Branch, CCR, NCI, NIH, Bethesda, Maryland, USA.
  • Pommier Y; Molecular Pharmacology Group, Developmental Therapeutics Branch, CCR, NCI, NIH, Bethesda, Maryland, USA.
  • Grammatikakis I; Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Lal A; Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Mol Cell Biol ; 44(2): 43-56, 2024.
Article en En | MEDLINE | ID: mdl-38347726
ABSTRACT
Transcription factors play key roles in development and disease by controlling gene expression. Forkhead box A1 (FOXA1), is a pioneer transcription factor essential for mouse development and functions as an oncogene in prostate and breast cancer. In colorectal cancer (CRC), FOXA1 is significantly downregulated and high FOXA1 expression is associated with better prognosis, suggesting potential tumor suppressive functions. We therefore investigated the regulation of FOXA1 expression in CRC, focusing on well-differentiated CRC cells, where FOXA1 is robustly expressed. Genome-wide RNA stability assays identified FOXA1 as an unstable mRNA in CRC cells. We validated FOXA1 mRNA instability in multiple CRC cell lines and in patient-derived CRC organoids, and found that the FOXA1 3'UTR confers instability to the FOXA1 transcript. RNA pulldowns and mass spectrometry identified Staufen1 (STAU1) as a potential regulator of FOXA1 mRNA. Indeed, STAU1 knockdown resulted in increased FOXA1 mRNA and protein expression due to increased FOXA1 mRNA stability. Consistent with these data, RNA-seq following STAU1 knockdown in CRC cells revealed that FOXA1 targets were upregulated upon STAU1 knockdown. Collectively, this study uncovers a molecular mechanism by which FOXA1 is regulated in CRC cells and provides insights into our understanding of the complex mechanisms of gene regulation in cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Transcriptoma Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Mol Cell Biol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Transcriptoma Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Mol Cell Biol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos