CCT2,即Chaperonin Containing TCP1 Subunit 2,是分子伴侣蛋白复合物的一个关键亚基,其功能是协助蛋白质正确折叠,维持细胞内稳态[4]。CCT2在多种生物学过程中发挥作用,包括细胞增殖、迁移、凋亡和信号传导等。CCT2的异常表达和功能失调与多种疾病的发生发展密切相关,包括癌症、神经退行性疾病和遗传性疾病等。
在癌症领域,CCT2的表达水平和功能与肿瘤的发生发展密切相关。研究发现,CCT2在乳腺癌、胶质母细胞瘤和甲状腺乳头状癌等肿瘤组织中高表达,并与肿瘤的恶性进展、转移和不良预后相关[1][2][3][7]。CCT2通过多种机制促进肿瘤的发生发展,例如激活JAK2/STAT3信号通路、影响KRAS蛋白的稳定性、调节EMT基因转录等[1][2][3]。
在神经退行性疾病领域,CCT2的异常表达和功能失调也与多种疾病的发生发展密切相关。研究发现,CCT2在阿尔茨海默病和缺血性脑损伤等神经退行性疾病中表达异常,并影响神经元的凋亡和自噬等过程[8][9]。CCT2的异常表达和功能失调可能通过影响蛋白质的折叠和稳定性、调节信号传导通路等机制导致神经退行性疾病的发生发展。
在遗传性疾病领域,CCT2的突变也与多种疾病的发生发展密切相关。研究发现,CCT2的突变导致Leber先天性黑内障的发生,这是一种遗传性视网膜变性病[5][6]。CCT2的突变可能通过影响分子伴侣复合物的稳定性和功能,导致蛋白质的异常折叠和聚集,从而引发Leber先天性黑内障的发生。
综上所述,CCT2作为一种重要的分子伴侣蛋白,其表达和功能的异常与多种疾病的发生发展密切相关。CCT2在癌症、神经退行性疾病和遗传性疾病等领域的研究,有助于深入理解其生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Chen, Xi, Ma, Chenao, Li, Yaming, Guo, Hong, Yang, Qifeng. 2024. Trim21-mediated CCT2 ubiquitination suppresses malignant progression and promotes CD4+T cell activation in breast cancer. In Cell death & disease, 15, 542. doi:10.1038/s41419-024-06944-8. https://pubmed.ncbi.nlm.nih.gov/39079960/
2. Zhao, Feihu, Yao, Zhong, Li, Yaquan, Li, Xingang, Chen, Anjing. 2024. Targeting the molecular chaperone CCT2 inhibits GBM progression by influencing KRAS stability. In Cancer letters, 590, 216844. doi:10.1016/j.canlet.2024.216844. https://pubmed.ncbi.nlm.nih.gov/38582394/
3. Liu, Weiping, Lin, Renzhi, Zhu, Chumeng, Gao, Qiangang, Zhong, Jijun. . CCT2 Regulates ZEB1-Induced EMT Gene Transcription to Promote the Metastasis and Tumorigenesis of Papillary Thyroid Carcinoma. In Discovery medicine, 36, 1819-1830. doi:10.24976/Discov.Med.202436188.168. https://pubmed.ncbi.nlm.nih.gov/39327245/
4. Lv, Wenming, Shi, Lin, Pan, Jiebing, Wang, Shengbao. 2022. Comprehensive prognostic and immunological analysis of CCT2 in pan-cancer. In Frontiers in oncology, 12, 986990. doi:10.3389/fonc.2022.986990. https://pubmed.ncbi.nlm.nih.gov/36119498/
5. Minegishi, Yuriko, Nakaya, Naoki, Tomarev, Stanislav I. . Mutation in the Zebrafish cct2 Gene Leads to Abnormalities of Cell Cycle and Cell Death in the Retina: A Model of CCT2-Related Leber Congenital Amaurosis. In Investigative ophthalmology & visual science, 59, 995-1004. doi:10.1167/iovs.17-22919. https://pubmed.ncbi.nlm.nih.gov/29450543/
6. Minegishi, Yuriko, Sheng, XunLun, Yoshitake, Kazutoshi, Hattori, Seisuke, Iwata, Takeshi. 2016. CCT2 Mutations Evoke Leber Congenital Amaurosis due to Chaperone Complex Instability. In Scientific reports, 6, 33742. doi:10.1038/srep33742. https://pubmed.ncbi.nlm.nih.gov/27645772/
7. Liu, Qiang, Qi, Yihang, Kong, Xiangyi, Fang, Yi, Wang, Jing. 2021. Molecular and Clinical Characterization of CCT2 Expression and Prognosis via Large-Scale Transcriptome Profile of Breast Cancer. In Frontiers in oncology, 11, 614497. doi:10.3389/fonc.2021.614497. https://pubmed.ncbi.nlm.nih.gov/33869000/
8. Kwon, Hyun Jung, Jeon, Hong Jun, Choi, Goang-Min, Kim, Dae Won, Moon, Seung Myung. 2023. Tat-CCT2 Protects the Neurons from Ischemic Damage by Reducing Oxidative Stress and Activating Autophagic Removal of Damaged Protein in the Gerbil Hippocampus. In Neurochemical research, 48, 3585-3596. doi:10.1007/s11064-023-03995-9. https://pubmed.ncbi.nlm.nih.gov/37561257/
9. Ma, Xueting, Feng, Yuxin, Quan, Xiangyu, Fu, Xueqi, Zeng, Linlin. 2023. Multi-omics analysis revealed the role of CCT2 in the induction of autophagy in Alzheimer's disease. In Frontiers in genetics, 13, 967730. doi:10.3389/fgene.2022.967730. https://pubmed.ncbi.nlm.nih.gov/36704351/