ISYNA1,也称为myo-肌醇-3-磷酸合酶1,是一种编码myo-肌醇合成途径中的关键限速酶的基因。myo-肌醇是细胞内信号传导和代谢的重要中间体,参与多种生物学过程,包括细胞增殖、凋亡、迁移、侵袭和干细胞特性维持。ISYNA1的表达和活性受多种因素的调控,包括DNA甲基化、转录因子和细胞内代谢状态。ISYNA1在多种癌症中发挥重要作用,其表达水平与肿瘤的预后和临床病理特征相关。ISYNA1的表达受多种转录因子的调控,包括E2F1、Rb和p53。E2F1可以直接结合ISYNA1启动子并激活其表达,而Rb可以抑制E2F1的活性,从而抑制ISYNA1的表达。p53也可以直接结合ISYNA1启动子并激活其表达,从而抑制肿瘤的生长[4,5]。此外,ISYNA1的表达还受DNA甲基化的调控。在脑组织中,ISYNA1启动子的5'-上游区域存在性别特异性差异甲基化,这可能与ISYNA1的表达水平相关[1]。ISYNA1的表达还与肿瘤的发生和发展相关。例如,在膀胱癌中,ISYNA1的表达水平显著升高,并与肿瘤的T分期和淋巴结转移相关[2]。ISYNA1的过表达可以促进肿瘤细胞的增殖和抑制凋亡,这可能与ISYNA1促进myo-肌醇合成和抑制Notch1信号通路有关[2,3]。在卵巢癌中,ISYNA1的表达水平与肿瘤的预后相关,ISYNA1的缺失可以促进肿瘤细胞的生长、迁移和侵袭,并增加干细胞的特性[3]。此外,ISYNA1的表达还与p53的表达相关,p53可以抑制ISYNA1的表达,从而抑制肿瘤的生长[5]。ISYNA1的表达还受细胞内代谢状态的调控。例如,在肌醇缺乏的情况下,细胞内的磷脂代谢和基因表达会发生显著变化,这可能与ISYNA1的缺失有关[6]。综上所述,ISYNA1是一种重要的基因,其表达和活性受多种因素的调控,包括DNA甲基化、转录因子和细胞内代谢状态。ISYNA1在多种癌症中发挥重要作用,其表达水平与肿瘤的预后和临床病理特征相关。ISYNA1的研究有助于深入理解myo-肌醇代谢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. Seelan, Ratnam S, Pisano, M Michele, Greene, Robert M, Casanova, Manuel F, Parthasarathy, Ranga N. . Differential methylation of the gene encoding myo-inositol 3-phosphate synthase (Isyna1) in rat tissues. In Epigenomics, 3, 111-24. doi:10.2217/epi.10.73. https://pubmed.ncbi.nlm.nih.gov/21841945/
2. Guo, Xi, Li, Hui-Huang, Hu, Jiao, Chen, Jin-Bo, Zu, Xiong-Bing. 2019. ISYNA1 is overexpressed in bladder carcinoma and regulates cell proliferation and apoptosis. In Biochemical and biophysical research communications, 519, 246-252. doi:10.1016/j.bbrc.2019.08.129. https://pubmed.ncbi.nlm.nih.gov/31495492/
3. Yang, Lingling, Yang, Muyao, Cui, Chenxi, Lang, Tingyuan, Zhou, Qi. 2023. The myo-inositol biosynthesis rate-limiting enzyme ISYNA1 suppresses the stemness of ovarian cancer via Notch1 pathway. In Cellular signalling, 107, 110688. doi:10.1016/j.cellsig.2023.110688. https://pubmed.ncbi.nlm.nih.gov/37105506/
4. Seelan, Ratnam S, Parthasarathy, Latha K, Parthasarathy, Ranga N. . E2F1 regulation of the human myo-inositol 1-phosphate synthase (ISYNA1) gene promoter. In Archives of biochemistry and biophysics, 431, 95-106. doi:. https://pubmed.ncbi.nlm.nih.gov/15464731/
5. Koguchi, Tomoyuki, Tanikawa, Chizu, Mori, Jinichi, Kojima, Yoshiyuki, Matsuda, Koichi. 2016. Regulation of myo-inositol biosynthesis by p53-ISYNA1 pathway. In International journal of oncology, 48, 2415-24. doi:10.3892/ijo.2016.3456. https://pubmed.ncbi.nlm.nih.gov/27035231/
6. Suliman, Mahmoud, Case, Kendall C, Schmidtke, Michael W, Onu, Chisom J, Greenberg, Miriam L. 2022. Inositol depletion regulates phospholipid metabolism and activates stress signaling in HEK293T cells. In Biochimica et biophysica acta. Molecular and cell biology of lipids, 1867, 159137. doi:10.1016/j.bbalip.2022.159137. https://pubmed.ncbi.nlm.nih.gov/35247568/