A1bg基因编码α-1-B-糖蛋白(Alpha-1-B Glycoprotein,A1BG),这是一种存在于血浆中的糖蛋白。A1BG属于免疫球蛋白超家族,具有五个免疫球蛋白样结构域,主要在肝脏中表达。A1BG在血浆中的浓度较高,占血浆蛋白总量的1-2%。其功能包括调节细胞生长和分化,参与免疫应答,以及作为细胞因子和激素的载体。此外,A1BG还可能参与血管生成、炎症反应和细胞信号传导等生物学过程。
A1BG在多种疾病中发挥重要作用。例如,A1BG在乳腺癌细胞中表达上调,与多柔比星(Adriamycin,ADR)耐药性相关。A1BG反义RNA 1(A1BG-AS1)通过招募胰岛素样生长因子2 mRNA结合蛋白2(IGF2BP2)并上调多药耐药相关蛋白1(ABCB1)的表达,从而增强乳腺癌细胞对ADR的耐药性[1]。A1BG-AS1还在骨肉瘤细胞中发挥作用,通过调节miR-148a-3p/USP22轴和稳定SIRT1的表达,促进骨肉瘤细胞的生长和侵袭[2]。在肝细胞癌(HCC)中,A1BG-AS1表达下调,其低表达与HCC患者的预后不良相关。A1BG-AS1通过直接结合miR-216a-5p,抑制HCC细胞的增殖、迁移和侵袭[3]。A1BG-AS1还在糖尿病足溃疡(DFU)中发挥作用,通过海绵化miR-214-3p影响血管生成相关基因的表达,抑制内皮细胞分化和增殖[4]。
在前列腺癌中,A1BG-AS1的表达受m6A甲基转移酶ZC3H13的调控。ZC3H13通过m6A修饰稳定A1BG-AS1的表达,从而抑制前列腺癌细胞的侵袭、迁移和增殖[5]。此外,A1BG在女性心脏中具有重要作用,其缺失会导致女性心脏功能障碍,表现为扩张型心肌病[6]。在乳腺癌中,A1BG-AS1通过海绵化miR-485-5p并上调FLOT1的表达,促进乳腺癌的发生和发展[7]。在宫颈癌中,A1BG的表达上调,可能作为宫颈癌的潜在生物标志物[8]。A1BG还与CRISP2蛋白相互作用,抑制CRISP2的甾醇结合和分泌功能,这可能与A1BG在癌症进展中的作用以及含有CRISP蛋白的爬行动物毒液的毒性有关[9]。
综上所述,A1bg基因编码的A1BG蛋白在多种生物学过程中发挥重要作用,包括细胞生长、分化、免疫应答、血管生成、炎症反应和细胞信号传导等。A1BG在多种疾病中发挥重要作用,如乳腺癌、骨肉瘤、HCC、DFU、前列腺癌、宫颈癌等。此外,A1BG还具有独立的染色质调控功能,影响基因表达和干细胞的多能性维持。A1bg基因的研究有助于深入理解A1BG蛋白的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. Wang, Jian, Xu, Jie, Zheng, Jie. 2023. A1BG-AS1 promotes adriamycin resistance of breast cancer by recruiting IGF2BP2 to upregulate ABCB1 in an m6A-dependent manner. In Scientific reports, 13, 20730. doi:10.1038/s41598-023-47956-2. https://pubmed.ncbi.nlm.nih.gov/38007504/
2. Han, Xiuxin, Yin, Mengfan, Gong, Chen, Wang, Guowen, Li, Lili. 2023. A1BG-AS1 promotes the biological functions of osteosarcoma cells via regulating the microRNA-148a-3p/USP22 axis and stabilizing the expression of SIRT1 through deubiquitinase function. In Expert opinion on therapeutic targets, 27, 1017-1029. doi:10.1080/14728222.2023.2263908. https://pubmed.ncbi.nlm.nih.gov/37747800/
3. Bai, Jigang, Yao, Bowen, Wang, Liang, Xu, Qiuran, Yang, Wei. 2018. lncRNA A1BG-AS1 suppresses proliferation and invasion of hepatocellular carcinoma cells by targeting miR-216a-5p. In Journal of cellular biochemistry, 120, 10310-10322. doi:10.1002/jcb.28315. https://pubmed.ncbi.nlm.nih.gov/30556161/
4. Wu, Fangfang, Wang, Lixia, Zuo, Hongju, Tian, Hanbing. 2025. LncRNA A1BG-AS1 regulates the progress of diabetic foot ulcers via sponging miR-214-3p. In Endocrine journal, 72, 295-306. doi:10.1507/endocrj.EJ24-0440. https://pubmed.ncbi.nlm.nih.gov/39779214/
5. Juneja, R K, Saha, N, Tay, J S, Low, P S, Gahne, B. . Distribution of plasma alpha-1-B-glycoprotein (A1BG) polymorphism in several populations of the Indian subcontinent. In Annals of human biology, 21, 443-8. doi:. https://pubmed.ncbi.nlm.nih.gov/7985993/
6. Yang, Zhi, Luo, Yu, Zhang, Fan, Ma, Likun. 2024. Exosome-derived lncRNA A1BG-AS1 attenuates the progression of prostate cancer depending on ZC3H13-mediated m6A modification. In Cell division, 19, 5. doi:10.1186/s13008-024-00110-4. https://pubmed.ncbi.nlm.nih.gov/38351022/
7. Emerson, James I, Shi, Wei, Conlon, Frank L. 2024. Sex-Specific Response to A1BG Loss Results in Female Dilated Cardiomyopathy. In Research square, , . doi:10.21203/rs.3.rs-4631369/v1. https://pubmed.ncbi.nlm.nih.gov/39070637/
8. Cai, Shibin, Zhou, Yi, Pan, Ying, Yu, Kaijie, Chen, Shuzheng. 2021. Long non-coding RNA A1BG-AS1 promotes tumorigenesis in breast cancer by sponging microRNA-485-5p and consequently increasing expression of FLOT1 expression. In Human cell, 34, 1517-1531. doi:10.1007/s13577-021-00554-8. https://pubmed.ncbi.nlm.nih.gov/34115333/
9. Canales, Norma Angélica Galicia, Marina, Vicente Madrid, Castro, Jorge Salmerón, Roman, Margarita Bahena, Castro-Romero, Julieta Ivone. 2014. A1BG and C3 are overexpressed in patients with cervical intraepithelial neoplasia III. In Oncology letters, 8, 939-947. doi:. https://pubmed.ncbi.nlm.nih.gov/25009667/