基因ACSM1,也称为酰基辅酶A合成酶中链家族成员1,是一种重要的酶,参与脂肪酸的代谢过程。ACSM1在脂肪酸的活化过程中起关键作用,将脂肪酸与辅酶A结合形成酰基辅酶A,从而进入三羧酸循环进行能量代谢。ACSM1主要表达在肝脏、心脏和肌肉等组织中,对维持机体能量平衡和脂肪酸代谢稳态至关重要。
在前列腺癌中,ACSM1的表达水平显著升高,与肿瘤的发生、发展和预后密切相关。研究表明,ACSM1通过促进脂肪酸氧化和能量代谢,为肿瘤细胞提供能量支持,从而促进肿瘤生长和侵袭[1]。此外,ACSM1还能抑制铁死亡,一种依赖于铁和脂质过氧化的细胞死亡方式,从而提高肿瘤细胞对放化疗的抵抗性[1]。因此,ACSM1被认为是前列腺癌治疗的一个潜在靶点。
除了在前列腺癌中的作用,ACSM1还与其他多种疾病相关。例如,在急性肾损伤中,ACSM1的表达水平降低,导致细胞对氧化应激和铁死亡的敏感性增加[2]。此外,ACSM1基因的变异与精神分裂症和重度抑郁症的发病风险相关[3]。在肝细胞癌中,ACSM1的表达水平升高,通过促进脂肪酸代谢和细胞增殖,加速肿瘤的进展[4]。
此外,ACSM1还与其他一些基因存在相互作用。例如,在乳腺导管癌中,ACSM1与15-前列腺素脱氢酶共同表达,定义了一种新的分子亚型[5]。在前列腺癌中,ACSM1与GRIN3A共同表达,与肿瘤的侵袭性和不良预后相关[6]。
综上所述,ACSM1在多种生物学过程中发挥重要作用,包括脂肪酸代谢、能量代谢、铁死亡和细胞增殖等。ACSM1的表达异常与多种疾病的发生、发展和预后密切相关,包括前列腺癌、急性肾损伤、精神分裂症、重度抑郁症和肝细胞癌等。因此,ACSM1被认为是疾病诊断、预后预测和治疗的一个重要靶点。未来的研究需要进一步探讨ACSM1的生物学功能和调控机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Shrestha, Raj K, Nassar, Zeyad D, Hanson, Adrienne R, Butler, Lisa M, Selth, Luke A. . ACSM1 and ACSM3 Regulate Fatty Acid Metabolism to Support Prostate Cancer Growth and Constrain Ferroptosis. In Cancer research, 84, 2313-2332. doi:10.1158/0008-5472.CAN-23-1489. https://pubmed.ncbi.nlm.nih.gov/38657108/
2. Zhang, Jing, Wei, Yuehan, Yue, Yangbo, Mou, Shan, Zhong, Qing. 2024. RIPK4 promotes oxidative stress and ferroptotic death through the downregulation of ACSM1. In Proceedings of the National Academy of Sciences of the United States of America, 121, e2410628121. doi:10.1073/pnas.2410628121. https://pubmed.ncbi.nlm.nih.gov/39316049/
3. Guo, Yongchen, Ren, Chunna, Huang, Wentao, Yang, Wancai, Bao, Yonghua. 2022. Oncogenic ACSM1 in prostate cancer is through metabolic and extracellular matrix-receptor interaction signaling pathways. In American journal of cancer research, 12, 1824-1842. doi:. https://pubmed.ncbi.nlm.nih.gov/35530294/
4. Li, Wenjin, Ji, Weidong, Li, Zhiqiang, Ji, Jue, Shi, Yongyong. 2015. Genetic association of ACSM1 variation with schizophrenia and major depressive disorder in the Han Chinese population. In American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 168B, 144-9. doi:10.1002/ajmg.b.32291. https://pubmed.ncbi.nlm.nih.gov/25656805/
5. Zhang, Limei, Wang, Jinfu, Gui, Fenfang, Deng, Weiping, Zhu, Qian. 2024. METTL3-mediated m6A modification of ZNF384 promotes hepatocellular carcinoma progression by transcriptionally activating ACSM1. In Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, , . doi:10.1007/s12094-024-03701-3. https://pubmed.ncbi.nlm.nih.gov/39342516/
6. Bailey, Peter S J, Hiltunen, J Kalervo, Dieckmann, Carol L, Kastaniotis, Alexander J, Nathan, James A. 2018. Different opinion on the reported role of Poldip2 and ACSM1 in a mammalian lipoic acid salvage pathway controlling HIF-1 activation. In Proceedings of the National Academy of Sciences of the United States of America, 115, E7458-E7459. doi:10.1073/pnas.1804041115. https://pubmed.ncbi.nlm.nih.gov/30042217/