SSR4,即信号序列受体蛋白4,是一种重要的蛋白质,在真核生物中发挥着多种生物学功能。SSR4作为信号序列受体复合物的一部分,参与蛋白质的跨膜转运,是蛋白质合成和加工过程中的关键因素。此外,SSR4还在基因表达调控中发挥作用,影响多种生物学过程,包括细胞分化、发育、代谢和疾病发生。
在人类疾病中,SSR4基因的变异与多种疾病相关,如先天性糖基化异常(CDG)和癌症。CDG是一组罕见的遗传性疾病,由于蛋白质和脂质的糖基化过程异常导致。SSR4基因的变异可以导致CDG-Iy型,这是一种X连锁遗传疾病,主要表现为神经发育迟缓、肌张力减退、小头畸形和面部特征异常等。已有研究表明,SSR4基因的变异会影响其蛋白表达和功能,导致蛋白质糖基化异常,进而影响细胞功能和器官发育[1,3,5,6,7,8,9]。
在癌症研究中,SSR4基因的表达与多种癌症的发生和发展相关。例如,在结直肠癌中,SSR4基因的高表达与肿瘤浸润淋巴细胞(TILs)的浸润相关,高表达的SSR4蛋白与淋巴结转移、远处转移、AJCC分期和RECIST疗效相关,提示SSR4可能作为结直肠癌的预后生物标志物[2]。此外,在食管鳞状细胞癌(ESCC)中,SSR4基因的过表达与临床病理因素相关,并且与肿瘤微环境(TME)的调节相关,可能作为ESCC的潜在诊断和靶向治疗生物标志物[4]。
综上所述,SSR4基因在真核生物中发挥着重要的生物学功能,其变异与多种疾病相关,包括先天性糖基化异常和癌症。SSR4基因的研究有助于深入理解其在疾病发生和发展中的作用,为疾病的诊断、治疗和预防提供新的思路和策略。
参考文献:
1. Wu, Ruohao, Tang, Wenting, Qiu, Kunyin, Li, Xiaojuan, He, Zhanwen. . [Analysis of SSR4 gene variant in a child with congenital glycosylation type 1y in conjunct with congenital dysplasia of external auditory canal]. In Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics, 39, 727-730. doi:10.3760/cma.j.cn511374-20210205-00114. https://pubmed.ncbi.nlm.nih.gov/35810430/
2. He, Weiwei, Wang, Bin, He, Jikai, Zhao, Youcai, Zhao, Wei. 2021. SSR4 as a prognostic biomarker and related with immune infiltration cells in colon adenocarcinoma. In Expert review of molecular diagnostics, 22, 223-231. doi:10.1080/14737159.2022.2019015. https://pubmed.ncbi.nlm.nih.gov/34904499/
3. Wang, Jun, Gou, Xingqing, Wang, Xiyi, Zhao, Nan, Wang, Xiaohong. 2022. Case Report: The novel hemizygous mutation in the SSR4 gene caused congenital disorder of glycosylation type iy: A case study and literature review. In Frontiers in genetics, 13, 955732. doi:10.3389/fgene.2022.955732. https://pubmed.ncbi.nlm.nih.gov/36386804/
4. Zhang, Jiaqi, Jia, Fang, Li, Chuqiao, Song, Shunzhe, Gong, Aixia. 2025. Unveiling SSR4: a promising biomarker in esophageal squamous cell carcinoma. In Frontiers in immunology, 16, 1544154. doi:10.3389/fimmu.2025.1544154. https://pubmed.ncbi.nlm.nih.gov/40066443/
5. Weng, Lingwei, Deng, Qingqing, Chen, Xiuli, Wang, Kai, Shao, Jie. . [A case of Congenital disorder of glycosylation due to SSR4 gene deletion]. In Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics, 40, 364-367. doi:10.3760/cma.j.cn511374-20210918-00762. https://pubmed.ncbi.nlm.nih.gov/36854416/
6. Johnsen, Christin, Tabatadze, Nazi, Radenkovic, Silvia, Melikishvili, Gia, Morava, Eva. 2024. SSR4-CDG, an ultra-rare X-linked congenital disorder of glycosylation affecting the TRAP complex: Review of 22 affected individuals including the first adult patient. In Molecular genetics and metabolism, 142, 108477. doi:10.1016/j.ymgme.2024.108477. https://pubmed.ncbi.nlm.nih.gov/38805916/
7. Sun, Wenqiang, Jin, Xinyun, Zhu, Xueping. 2024. A novel SSR4 variant associated with congenital disorder of glycosylation: a case report and related analysis. In Frontiers in genetics, 15, 1402883. doi:10.3389/fgene.2024.1402883. https://pubmed.ncbi.nlm.nih.gov/39086474/
8. Wang, Quanquan, Wang, Guangyu, Liang, Bing, Lin, Pengfei, Li, Ling. 2024. Intron retention caused by a canonical splicing variant in SSR4-related congenital disorder of glycosylation. In Journal of human genetics, 70, 171-176. doi:10.1038/s10038-024-01309-7. https://pubmed.ncbi.nlm.nih.gov/39653760/
9. Ng, Bobby G, Raymond, Kimiyo, Kircher, Martin, Gibson, James B, Freeze, Hudson H. 2015. Expanding the Molecular and Clinical Phenotype of SSR4-CDG. In Human mutation, 36, 1048-51. doi:10.1002/humu.22856. https://pubmed.ncbi.nlm.nih.gov/26264460/