Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Long noncoding RNAs (lncRNAs) are emerging as critical regulators in tumor initiation and progression. However, the biological mechanisms and potential clinical application of lncRNA NORAD in endometrial cancer (EC) remain unknown. Herein, we identified NORAD underwent promoter hypermethylation-associated downregulation in EC. Epigenetic inactivation of NORAD was correlated with EC progression (FIGO stage) and poor outcome. Overexpression of NORAD significantly inhibited cell growth and promoted apoptosis in EC cells. Mechanistic studies revealed that multiple regions of NORAD served as a platform for binding with the central domain of anti-apoptotic factor FUBP1. Our findings further indicated that the NORAD/FUBP1 interaction attenuated FUBP1 nuclear localization and thus impaired the occupancies of FUBP1 on its target pro-apoptotic gene promoters, resulting in apoptosis induction in EC. Moreover, knockdown of NORAD promoted tumor growth in the xenograft mice model. While, introduction of NORAD-4 fragment, which bound with FUBP1, successfully reversed tumor growth and apoptosis inhibition mediated by NORAD knockdown in vivo. Our findings provide mechanistic insight into the critical roles of NORAD as a tumor suppressor in EC progression. NORAD could possibly serve as a novel prognostic biomarker and provide the rationale for EC therapy.
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PMID:NORAD orchestrates endometrial cancer progression by sequestering FUBP1 nuclear localization to promote cell apoptosis. 3255 78