IMPA2(inositol monophosphatase 2)是肌醇单磷酸酶2的基因,编码肌醇单磷酸酶2蛋白。肌醇单磷酸酶2是肌醇代谢途径中的关键酶之一,参与肌醇-1,4,5-三磷酸(IP3)的合成和降解,IP3是细胞内第二信使,参与调控细胞内的钙离子浓度,进而影响多种细胞功能,如细胞增殖、迁移、凋亡等。IMPA2基因位于18号染色体短臂,基因长度约为12kb,包含8个外显子和7个内含子。
IMPA2基因在多种肿瘤的发生发展中发挥重要作用。例如,在结直肠癌中,IMPA2基因的表达水平显著下调,与患者的预后不良相关[1]。IMPA2基因的低表达与肿瘤的分期、分级、淋巴结转移和远处转移等因素相关,提示IMPA2基因可能作为结直肠癌的预后标志物。IMPA2基因的低表达与脂质代谢和上皮间质转化(EMT)等过程相关,这些过程在肿瘤的发生发展中发挥重要作用。此外,IMPA2基因的表达受到DNA甲基化的调控,提示DNA甲基化可能参与IMPA2基因表达的调控。
在乳腺癌中,IMPA2基因的表达水平显著上调,与肿瘤的侵袭性和预后不良相关[2]。IMPA2基因的表达上调与MYC基因的表达上调相关,形成正反馈回路,增强肿瘤细胞的侵袭性。IMPA2基因的敲低可以抑制肿瘤细胞的增殖、迁移和侵袭,提示IMPA2基因可能作为乳腺癌的治疗靶点。
在宫颈癌中,IMPA2基因的表达水平上调,促进肿瘤细胞的增殖和迁移,抑制肿瘤细胞的凋亡[3][4]。IMPA2基因的敲低可以抑制肿瘤细胞的增殖、迁移和侵袭,增强肿瘤细胞对化疗药物的敏感性。IMPA2基因通过MAPK信号通路和p53-AIFM2信号通路调节肿瘤细胞的增殖、迁移和凋亡,提示IMPA2基因可能作为宫颈癌的治疗靶点。
IMPA2基因还与精神疾病的发生发展相关。例如,在双相情感障碍(BPD)中,IMPA2基因的多态性与疾病的易感性相关[5][6]。IMPA2基因的启动子区域的多态性rs2075824与疾病的发病年龄相关,提示IMPA2基因可能参与疾病的发生发展。IMPA2基因的表达水平与钙离子浓度相关,提示IMPA2基因可能参与疾病的神经生物学机制[7][8]。
综上所述,IMPA2基因在肿瘤和精神疾病的发生发展中发挥重要作用。IMPA2基因的表达水平、多态性和功能与多种生物学过程相关,包括细胞增殖、迁移、凋亡、脂质代谢、上皮间质转化、钙离子浓度等。IMPA2基因可能作为肿瘤和精神疾病的诊断、预后和治疗靶点,为疾病的防治提供新的思路和策略。
参考文献:
1. Wang, Liuli, Liu, Deming, Liu, Shuo, Ma, Haizhong, Cai, Hui. 2022. Identification of IMPA2 as the hub gene associated with colorectal cancer and liver metastasis by integrated bioinformatics analysis. In Translational oncology, 21, 101435. doi:10.1016/j.tranon.2022.101435. https://pubmed.ncbi.nlm.nih.gov/35483170/
2. Lei, Xingyu, Liao, Ruocen, Chen, Xingyu, Dai, Zhijun, Dong, Chenfang. 2023. IMPA2 promotes basal-like breast cancer aggressiveness by a MYC-mediated positive feedback loop. In Cancer letters, 582, 216527. doi:10.1016/j.canlet.2023.216527. https://pubmed.ncbi.nlm.nih.gov/38048842/
3. Xie, Kexin, Liu, Lei, Wang, Min, Lin, Yingrui, Zhu, Xiaolin. . IMPA2 blocks cervical cancer cell apoptosis and induces paclitaxel resistance through p53-mediated AIFM2 regulation. In Acta biochimica et biophysica Sinica, 55, 623-632. doi:10.3724/abbs.2023069. https://pubmed.ncbi.nlm.nih.gov/37140233/
4. Zhang, Kan, Liu, Lei, Wang, Min, Tan, Shan, Luo, Lingli. 2020. A novel function of IMPA2, plays a tumor-promoting role in cervical cancer. In Cell death & disease, 11, 371. doi:10.1038/s41419-020-2507-z. https://pubmed.ncbi.nlm.nih.gov/32409648/
5. Bloch, Paul J, Weller, Andrew E, Doyle, Glenn A, Hodge, Rachel, Lohoff, Falk W. 2010. Association analysis between polymorphisms in the myo-inositol monophosphatase 2 (IMPA2) gene and bipolar disorder. In Progress in neuro-psychopharmacology & biological psychiatry, 34, 1515-9. doi:10.1016/j.pnpbp.2010.08.015. https://pubmed.ncbi.nlm.nih.gov/20800640/
6. Tomioka, Yoko, Jiménez, Esther, Salagre, Estela, Benabarre, Antoni, Grande, Iria. 2018. Association between genetic variation in the myo-inositol monophosphatase 2 (IMPA2) gene and age at onset of bipolar disorder. In Journal of affective disorders, 232, 229-236. doi:10.1016/j.jad.2018.02.002. https://pubmed.ncbi.nlm.nih.gov/29499505/
7. Yoshikawa, T, Kikuchi, M, Saito, K, Toru, M, Detera-Wadleigh, S D. . Evidence for association of the myo-inositol monophosphatase 2 (IMPA2) gene with schizophrenia in Japanese samples. In Molecular psychiatry, 6, 202-10. doi:. https://pubmed.ncbi.nlm.nih.gov/11317223/
8. Li, Jia, Huang, Sheng, Dai, Hui-Rong, Yuan, Jian-Min, Li, Li. 2016. A promoter polymorphism rs2075824 within IMPA2 gene affecting the transcription activity: possible relationship with schizophrenia. In Journal of cellular and molecular medicine, 21, 658-664. doi:10.1111/jcmm.13009. https://pubmed.ncbi.nlm.nih.gov/27748550/