Characterisation of APOBEC3B-Mediated RNA editing in breast cancer cells reveals regulatory roles of NEAT1 and MALAT1 lncRNAs.

Autor: Zhang C; Centre for Cancer Drug Discovery, The Institute of Cancer Research, London, UK.; Shanghai Institute of Biological Products, Shanghai, China., Lu YJ; Guangdong Medicine-Engineering Interdisciplinary Technology Research Centre, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China., Wang M; Shanghai Institute of Biological Products, Shanghai, China., Chen B; Centre for Cancer Drug Discovery, The Institute of Cancer Research, London, UK.; GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China., Xiong F; Shanghai Institute of Biological Products, Shanghai, China., Mitsopoulos C; Centre for Cancer Drug Discovery, The Institute of Cancer Research, London, UK., Rossanese O; Centre for Cancer Drug Discovery, The Institute of Cancer Research, London, UK., Li X; Shanghai Institute of Biological Products, Shanghai, China. lixiuling@sinopharm.com., Clarke PA; Centre for Cancer Drug Discovery, The Institute of Cancer Research, London, UK. paul.clarke@icr.ac.uk.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2024 Nov; Vol. 43 (46), pp. 3366-3377. Date of Electronic Publication: 2024 Sep 25.
DOI: 10.1038/s41388-024-03171-5
Abstrakt: RNA editing is a crucial post-transcriptional process that influences gene expression and increases the diversity of the proteome as a result of amino acid substitution. Recently, the APOBEC3 family has emerged as a significant player in this mechanism, with APOBEC3A (A3A) having prominent roles in base editing during immune and stress responses. APOBEC3B (A3B), another family member, has gained attention for its potential role in generating genomic DNA mutations in breast cancer. In this study, we coupled an inducible expression cell model with a novel methodology for identifying differential variants in RNA (DVRs) to map A3B-mediated RNA editing sites in a breast cancer cell model. Our findings indicate that A3B engages in selective RNA editing including targeting NEAT1 and MALAT1 long non-coding RNAs that are often highly expressed in tumour cells. Notably, the binding of these RNAs sequesters A3B and suppresses global A3B activity against RNA and DNA. Release of A3B from NEAT1/MALAT1 resulted in increased A3B activity at the expense of A3A activity suggesting a regulatory feedback loop between the two family members. This research substantially advances our understanding of A3B's role in RNA editing, its mechanistic underpinnings, and its potential relevance in the pathogenesis of breast cancer.
Competing Interests: Competing interests CZ, KM, OR, and PAC are current or past employees of The Institute of Cancer Research, which has a commercial interest in the discovery and development of A3B inhibitors and operates a reward to inventors’ scheme. Separately, CZ, MW, FX, and XL are employees of Shanghai Institute of Biological Products, an entity presently engaged in the commercial development of therapeutic biologics. No conflicts of interest have been reported by the remaining authors. Ethics approval and consent to participate The authors confirm that all methods were performed in accordance with the relevant guidelines and regulations.
(© 2024. The Author(s).)
Databáze: MEDLINE
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