Evaluation of Circ_0000977-Mediated Regulatory Network in Breast Cancer: A Potential Discriminative Biomarker for Triple-Negative Tumors.

Autor: Darbeheshti F; Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.; Medical Genetics Network (MeGeNe), Universal Scientific Education and Research Network (USERN), Tehran, Iran., Mansoori Y; Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran.; Department of Medical Genetics, Fasa University of Medical Sciences, Fasa, Iran., Azizi-Tabesh G; Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Zolfaghari F; Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran., Kadkhoda S; Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran., Rasti A; Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran., Rezaei N; Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Dr. Qarib St, Keshavarz Blvd, Tehran, Iran. rezaei_nima@tums.ac.ir.; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. rezaei_nima@tums.ac.ir.; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran. rezaei_nima@tums.ac.ir., Shakoori A; Medical Genetic Ward, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Dr. Qarib St, Keshavarz Blvd, Tehran, Iran. shakooria@sina.tums.ac.ir.; Breast Disease Research Center (BDRC), Tehran University of Medical Sciences, Tehran, Iran. shakooria@sina.tums.ac.ir.
Jazyk: angličtina
Zdroj: Biochemical genetics [Biochem Genet] 2023 Aug; Vol. 61 (4), pp. 1487-1508. Date of Electronic Publication: 2023 Jan 16.
DOI: 10.1007/s10528-023-10331-x
Abstrakt: Previous investigations have revealed that circular RNAs (circRNAs) play pivotal roles in cancer development and progression by participating in several biological procedures, such as competing endogenous RNA (ceRNA) networks. Recently, circRNAs have been proposed as non-invasive, stable, and affordable cell-free biomarkers for cancer screening and test monitoring. Although, their clinical usefulness vastly remains to be evaluated in breast cancer (BC). Triple-negative breast cancer (TNBC), as the most challenging BC subtype, is an urgent requirement of identifying specific biomarkers and discovering the molecular mechanisms that lead to aggressive behaviors of tumor cells. The therapeutic strategies for TN patients have remained limited due to the impracticality of endocrine therapies and a remarkable portion of patients with TNBC experience recurrence, chemoresistance, and metastasis. TNBC Microarray expression profile analysis found that circ_0000977 is one of the most dysregulated circRNA in TNBC in comparison with non-TNBC. It could be a clue referring to the potential clinical utility of circ_0000977 in TNBC. The current study aims to assess the clinical implications and potential ceRNA regulatory network of circ_0000977 in TNBC. We confirmed circ_0000977 down-regulation in TNBC cell lines and tumors versus non-TNBC samples by real-time PCR. Subsequently, an assessment of the diagnostic value of circ_0000977 in plasma samples from triple-negative patients revealed a potential diagnostic cell-free biomarker in triple-negative BC. Finally, our integrative approach uncovered potential circ-0000977/miR-135b-5p/mRNAs regulatory network in TNBC. The inhibitory effect of miR-135b-5p on its downstream mRNAs was assessed by knocking down it in MDA-MB-231 cells. Functional and correlation analyses revealed APC and GATA3 could be regulated by circ_0000977/miR-135b-5p ceRNA axis, which presents valuable insight into circ-0000977-mediated gene silencing involved in the ceRNA network of TNBC. This study uncovered the potential clinical implication of circ_0000977 for the diagnosis and treatment of TNBC patients.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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