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Circular Rna-Associated Cerna Network Involved in Hif-1 Signalling in Triple-Negative Breast Cancer: Circ_0047303 As a Potential Key Regulator Publisher Pubmed



Darbeheshti F1, 2 ; Mahdiannasser M2 ; Noroozi Z3 ; Firoozi Z1 ; Mansoori B4 ; Daraei A5 ; Bastami M6 ; Narimansalehfam Z7 ; Valipour E2 ; Mansoori Y1, 6
Authors
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Authors Affiliations
  1. 1. Department of Medical Genetics, Fasa University of Medical Sciences, Fasa, Iran
  2. 2. Department of Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of General Surgery, Fasa University of Medical Sciences, Fasa, Iran
  5. 5. Department of Medical Genetics, School of Medicine, Babol University of Medical Sciences, Babol, Iran
  6. 6. Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
  7. 7. Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Source: Journal of Cellular and Molecular Medicine Published:2021


Abstract

The aggressive and highly metastatic nature of triple-negative breast cancer (TNBC) causes patients to suffer from the poor outcome. HIF-1 signalling pathway is a prominent pathway that contributes to angiogenesis and metastasis progression in tumours. On the contrary, the undeniable importance of circular RNAs (circRNAs) as multifunctional non-coding RNAs (ncRNAs) has been identified in breast cancer. These ncRNAs owing to their high stability and specificity have been becoming a hotspot in cancer researches. circRNAs act as competing endogenous RNAs (ceRNAs) and compete with mRNAs for shared miRNAs, thus modulate gene expression. Since the most dysregulated biological functions in TNBC are associated with cellular invasion, understanding the molecular pathogenesis of these processes is a crucial step towards the development of new treatment approaches. The purpose of this study is to undermine the circRNA-associated ceRNA network involved in HIF-1 signalling in TNBC using an integrative bioinformatics approach. In the next step, the novel circ_0047303-mediated ceRNA regulatory axes have been extracted and validated across TNBC samples. We show that circ_0047303 has the highest degree in the circRNA-associated ceRNA network and shows a significant up-expression in TNBC. Moreover, our results suggest that circ_0047303 could mediate the upregulation of key angiogenesis-related genes, including HIF-1, EIF4E2 and VEGFA in TNBC through sponging the tumour-suppressive miRNAs. The circ_0047303 could be a promising molecular biomarker and/or therapeutic target for TNBC. © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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