Ccnd1, which encodes the protein cyclin D1, is responsible for regulating the G1 to S phase transition in the cell cycle [3]. This regulation is a crucial part of the normal cell cycle progression pathway, and thus Ccnd1 is of great biological importance in cell proliferation processes. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, can be valuable for studying Ccnd1's functions.

In various cancers, Ccnd1 has been implicated in different aspects. In gastric cancer, a circular RNA, circNFATC3, promotes cancer cell proliferation by binding to IGF2BP3, enhancing CCND1 mRNA stability through preventing IGF2BP3 ubiquitination [1]. In low-grade glioma, CCND1 is a prognosis-related gene with differential expression in tumor and normal samples, and high-expression levels are beneficial for survival in advanced cases [2]. In breast cancer, CCND1 amplification is significantly associated with positive estrogen receptor status, cyclin D1 overexpression, shorter recurrence-free survival (RFS) and overall survival (OS), especially in endocrine-therapy-treated patients [3]. In endometrial cancer, CCND1 overexpression is correlated with lymph node metastasis, and it may promote autophagy which contributes to this metastasis [4]. Also, in head and neck potentially malignant disorders, CCND1 amplification/cyclin D1 overexpression is associated with the progression to head and neck squamous cell carcinoma [5]. In luminal B breast cancer, CCND1 copy number variation (CNV) in circulating tumor DNA (ctDNA) is associated with poor prognosis [6]. Even in idiopathic dilated cardiomyopathy, CCND1 is overexpressed, potentially contributing to disease progression [7].

In conclusion, Ccnd1 is essential for regulating the cell cycle. Through model-based research, its role in multiple diseases, especially various cancers, has been revealed. Studies on Ccnd1 using KO/CKO mouse models could potentially provide more insights into these disease mechanisms, offering new directions for disease treatment and prevention in cancer and cardiomyopathy areas.

References:

1. Yang, Feifei, Ma, Qiang, Huang, Bo, Li, Wei, Xiao, Bin. 2023. CircNFATC3 promotes the proliferation of gastric cancer through binding to IGF2BP3 and restricting its ubiquitination to enhance CCND1 mRNA stability. In Journal of translational medicine, 21, 402. doi:10.1186/s12967-023-04235-y. https://pubmed.ncbi.nlm.nih.gov/37340423/

2. Zhao, Kun, Zhang, Hui, Lin, Jianyang, Wei, Wenxiang, Wang, Yuanwei. 2024. Radiomic Prediction of CCND1 Expression Levels and Prognosis in Low-grade Glioma Based on Magnetic Resonance Imaging. In Academic radiology, 31, 4595-4610. doi:10.1016/j.acra.2024.03.031. https://pubmed.ncbi.nlm.nih.gov/38824087/

3. Jeffreys, Sarah A, Becker, Therese M, Khan, Sarah, de Souza, Paul, Powter, Branka. 2022. Prognostic and Predictive Value of CCND1/Cyclin D1 Amplification in Breast Cancer With a Focus on Postmenopausal Patients: A Systematic Review and Meta-Analysis. In Frontiers in endocrinology, 13, 895729. doi:10.3389/fendo.2022.895729. https://pubmed.ncbi.nlm.nih.gov/35784572/

4. Su, Yi, Zhou, Haonan, Ma, Zhao, Liu, Jing, Li, Chen. 2023. CCND1-Induced Autophagy Contributes to Lymph Node Metastasis in Endometrial Cancer. In Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 55, 413-419. doi:10.1055/a-2044-9227. https://pubmed.ncbi.nlm.nih.gov/37019147/

5. Ramos-García, Pablo, González-Moles, Miguel Ángel, Ayén, Ángela, Gil-Montoya, José Antonio, Ruiz-Ávila, Isabel. 2019. Predictive value of CCND1/cyclin D1 alterations in the malignant transformation of potentially malignant head and neck disorders: Systematic review and meta-analysis. In Head & neck, 41, 3395-3407. doi:10.1002/hed.25834. https://pubmed.ncbi.nlm.nih.gov/31184805/

6. Shimazaki, Akiko, Kubo, Makoto, Kurata, Kanako, Kai, Masaya, Nakamura, Masafumi. . CCND1 Copy Number Variation in Circulating Tumor DNA from Luminal B Breast Cancer Patients. In Anticancer research, 42, 4071-4077. doi:10.21873/anticanres.15904. https://pubmed.ncbi.nlm.nih.gov/35896251/

7. Dehghani, Khatereh, Stanek, Agata, Bagherabadi, Arash, Bagheri, Soghra, Zolghadri, Samaneh. 2023. CCND1 Overexpression in Idiopathic Dilated Cardiomyopathy: A Promising Biomarker? In Genes, 14, . doi:10.3390/genes14061243. https://pubmed.ncbi.nlm.nih.gov/37372424/