BCAS3,全称为Breast Carcinoma Amplified Sequence 3,是一种在人类染色体17q23区域发现的基因。该基因编码一种核蛋白,其功能与细胞迁移、血管生成以及癌症发展相关。BCAS3的表达模式在正常发育和肿瘤发生中均有体现,例如在胚胎干细胞和血管祖细胞中均有表达,提示其可能参与人类胚胎发生和肿瘤血管生成[5]。此外,BCAS3的表达还受到雌激素受体α(ERα)的调控,并通过与PELP1(proline-, glutamic acid-, and leucine-rich protein-1)的相互作用,激活其表达,发挥ERα的共激活因子作用[6]。
在癌症研究领域,BCAS3的功能和表达模式引起了广泛关注。研究发现,BCAS3在头颈鳞状细胞癌(HNSCC)中显著过表达,并且其表达与患者的临床病理特征和预后相关,提示BCAS3可能参与肿瘤的侵袭性和进展[1]。此外,BCAS3在乳腺癌中也表现出过表达和融合现象,提示其在乳腺癌的发生和发展中可能发挥重要作用[7]。在胶质母细胞瘤(GBM)中,BCAS3的表达上调与不良预后相关,并且BCAS3通过抑制p53/GADD45α信号通路,促进GBM细胞的增殖和细胞周期进展[4]。
除了在癌症中的研究,BCAS3还在其他生物学过程中发挥重要作用。例如,在秀丽隐杆线虫(C.elegans)中,BCAS3的同源基因myt-1的缺失会导致寿命缩短和氧化应激下的生存能力下降。MYTHO蛋白(由C16ORF70基因编码)在促进自噬和健康衰老中起重要作用,其通过结合WIPI2和BCAS3来招募和组装自噬小体的形成[2]。此外,BCAS3还与KinkyA蛋白相互作用,共同定位于早期自噬小体,并调节自噬过程[3]。
综上所述,BCAS3是一种多功能的基因,在正常发育、肿瘤发生、自噬和衰老等生物学过程中均发挥重要作用。BCAS3的表达和功能异常与多种疾病的发生和发展相关,因此,BCAS3可能成为疾病诊断和治疗的潜在靶点。未来研究需要进一步深入探讨BCAS3在各个生物学过程中的具体作用机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Challa, Devanand, Pandi, Chandra, Kannan, Balachander, Priyadharsini, Vijayashree J, Arumugam, Paramasivam. 2023. Exploring the Expression of BCAS3 in Head and Neck Squamous Cell Carcinoma and Its Association With Prognosis. In Cureus, 15, e50995. doi:10.7759/cureus.50995. https://pubmed.ncbi.nlm.nih.gov/38259392/
2. Franco-Romero, Anais, Morbidoni, Valeria, Milan, Giulia, Trevisson, Eva, Sandri, Marco. 2024. C16ORF70/MYTHO promotes healthy aging in C.elegans and prevents cellular senescence in mammals. In The Journal of clinical investigation, 134, . doi:10.1172/JCI165814. https://pubmed.ncbi.nlm.nih.gov/38869949/
3. Yamada, Yoko, Schaap, Pauline. 2020. The proppin Bcas3 and its interactor KinkyA localize to the early phagophore and regulate autophagy. In Autophagy, 17, 640-655. doi:10.1080/15548627.2020.1725403. https://pubmed.ncbi.nlm.nih.gov/32116088/
4. Wang, Yixuan, Li, Yuntao, Sun, Qian, Chen, Qianxue, Liu, Baohui. 2022. BCAS3 accelerates glioblastoma tumorigenesis by restraining the P53/GADD45α signaling pathway. In Experimental cell research, 417, 113231. doi:10.1016/j.yexcr.2022.113231. https://pubmed.ncbi.nlm.nih.gov/35659972/
5. Siva, Kavitha, Venu, Parvathy, Mahadevan, Anita, S K, Shankar, Inamdar, Maneesha S. 2007. Human BCAS3 expression in embryonic stem cells and vascular precursors suggests a role in human embryogenesis and tumor angiogenesis. In PloS one, 2, e1202. doi:. https://pubmed.ncbi.nlm.nih.gov/18030336/
6. Gururaj, Anupama E, Peng, Shaohua, Vadlamudi, Ratna K, Kumar, Rakesh. 2007. Estrogen induces expression of BCAS3, a novel estrogen receptor-alpha coactivator, through proline-, glutamic acid-, and leucine-rich protein-1 (PELP1). In Molecular endocrinology (Baltimore, Md.), 21, 1847-60. doi:. https://pubmed.ncbi.nlm.nih.gov/17505058/
7. Bärlund, Maarit, Monni, Outi, Weaver, J Donald, Kallioniemi, Olli-P, Kallioniemi, Anne. . Cloning of BCAS3 (17q23) and BCAS4 (20q13) genes that undergo amplification, overexpression, and fusion in breast cancer. In Genes, chromosomes & cancer, 35, 311-7. doi:. https://pubmed.ncbi.nlm.nih.gov/12378525/