Journal Article

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

Shi, Wenjing, Lei, Huiwen, Ma, Fengdie, Zhang, Taotao, Di, Cuixia, Shi, Maoning, Wang, Jing, Su, Wei, Xie, Xiaodong, Zhang, Shasha

2023

Overview

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.

• Publisher: Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
• Subject: 631/337 / 631/67 / 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