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Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Super-enhancer-driven ITGB2-AS1 promotes ovarian cancer progression by binding to IQGAP1
1Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Abstract:
Long non-coding RNAs (lncRNAs) are involved in the development and progression of ovarian cancer (OC). Super-enhancers play vital roles in epigenomic regulation. We investigated the functions and mechanisms of the super-enhancer-driven OC-specific lncRNA ITGB2-AS1. In this study, we revealed that the lncRNA ITGB2-AS1 was abnormally expressed in OC tissues and cells and was associated with poor prognosis. In vitro, ITGB2-AS1 silencing attenuated the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of SKOV3 and A2780 cells, whereas ITGB2-AS1 overexpression showed the opposite effect. ITGB2-AS1 inhibition in SKOV3 cells reduced tumor growth and EMT progression in vivo. Further analysis revealed that the transcription factor TFAP2C acts on a specific super-enhancer and drives ITGB2-AS1 to activate transcription. `ITGB2-AS1 directly binds to IQGAP1 protein, positively regulates its expression, and activates the canonical Wnt/β-catenin signaling pathway. The TFAP2C / ITGB2-AS1 / IQGAP1 / β-catenin axis may be a potential target for OC treatment.
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