Aberrant Cyclin D1 splicing in cancer: from molecular mechanism to therapeutic modulation

Cyclin D1 (CCND1), a crucial mediator of cell cycle progression, possesses many mutation types with different mutation frequencies in human cancers. The G870A mutation is the most common mutation in CCND1 , which produces two isoforms: full-length CCND1a and divergent C-terminal CCND1b. The dysregul...

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Bibliographic Details
Published in:Cell death & disease 2023-04, Vol.14 (4), p.244-244, Article 244
Main Authors: Wang, Jing, Su, Wei, Zhang, Taotao, Zhang, Shasha, Lei, Huiwen, Ma, Fengdie, Shi, Maoning, Shi, Wenjing, Xie, Xiaodong, Di, Cuixia
Format: Article
Language:English
Subjects:
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Antibodies
Biochemistry
Biomedical and Life Sciences
Cancer
Cancer therapies
CCND1 gene
Cell Biology
Cell Culture
Cell cycle
Chemotherapy
Cyclin D1
Cyclin D1 - genetics
Cyclin D1 - metabolism
Genetic Predisposition to Disease
Humans
Immunology
Isoforms
Life Sciences
Metastases
Mutation
Neoplasms - genetics
Neoplasms - therapy
Polymorphism, Single Nucleotide
Radiation therapy
Regulatory sequences
Review
Review Article
RNA Splicing
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Summary:Cyclin D1 (CCND1), a crucial mediator of cell cycle progression, possesses many mutation types with different mutation frequencies in human cancers. The G870A mutation is the most common mutation in CCND1 , which produces two isoforms: full-length CCND1a and divergent C-terminal CCND1b. The dysregulation of the CCND1 isoforms is associated with multiple human cancers. Exploring the molecular mechanism of CCND1 isoforms has offer new insight for cancer treatment. On this basis, the alterations of CCND1 gene are described, including amplification, overexpression, and mutation, especially the G870A mutation. Subsequently, we review the characteristics of CCND1 isoforms caused by G870A mutation. Additionally, we summarize cis-regulatory elements, trans-acting factors, and the splice mutation involved in splicing regulation of CCND1. Furthermore, we highlight the function of CCND1 isoforms in cell cycle, invasion, and metastasis in cancers. Importantly, the clinical role of CCND1 isoforms is also discussed, particularly concerning prognosis, chemotherapy, and radiotherapy. Last, emphasis is given to the corrective strategies that modulate the cancerous CCND1 isoforms. Thus, it is highlighting significance of aberrant isoforms of CCND1 as targets for cancer therapy.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-023-05763-7