Loxl4,也称为Lysyl oxidase like 4,是一种重要的细胞外基质蛋白,属于赖氨酰氧化酶家族。赖氨酰氧化酶家族是一组含铜的赖氨酰酪氨酸醌辅因子胺氧化酶,在细胞外基质的组装和维持中发挥着关键作用。Loxl4通过催化赖氨酰残基的交联,增强细胞外基质的稳定性和机械强度。Loxl4的表达受到多种因素的调控,包括转录因子、信号通路和细胞外环境等。Loxl4在多种生物学过程中发挥作用,包括组织修复、伤口愈合、血管生成和癌症发生等。
根据检索到的参考文献,Loxl4在多种疾病中发挥重要作用。在主动脉瘤方面,Loxl4的敲除并没有加剧小鼠由血管紧张素II诱导的胸主动脉瘤和腹主动脉瘤的形成,这表明Loxl4可能在主动脉瘤的发生发展中并不起主要作用[1]。在肝细胞癌方面,Loxl4的表达水平与预后呈正相关,Loxl4的下调与肿瘤的侵袭性和临床预后较差相关[2]。此外,Loxl4还可以通过促进细胞迁移和侵袭,以及促进血管生成,从而促进肝细胞癌的进展[3]。在膀胱癌方面,Loxl4基因是miR-193a-3p的直接靶基因,miR-193a-3p通过靶向Loxl4基因和氧化应激通路,调控膀胱癌的耐药性[4]。在头颈鳞状细胞癌方面,Loxl4基因的过表达与局部淋巴结转移和肿瘤分期相关,并且Loxl4基因的扩增在头颈鳞状细胞癌细胞系中常见[5]。在胃癌方面,Loxl4的表达上调与肿瘤大小、侵袭深度、淋巴结转移、TNM分期和较差的总体生存率相关,Loxl4通过激活FAK/Src通路促进胃癌细胞的增殖和转移[6]。在局灶性节段性肾小球硬化症(FSGS)方面,Loxl4基因的异种变异可能是FSGS的候选基因之一[7]。在乳腺癌方面,Loxl4的低表达与较差的总体生存率相关,并且Loxl4的下调通过诱导胶原合成、沉积和结构变化,促进肿瘤的生长和转移[8]。
综上所述,Loxl4在多种疾病中发挥重要作用,包括主动脉瘤、肝细胞癌、膀胱癌、头颈鳞状细胞癌、胃癌、FSGS和乳腺癌等。Loxl4的表达水平和功能受到多种因素的调控,包括转录因子、信号通路和细胞外环境等。Loxl4的研究有助于深入理解细胞外基质蛋白在疾病发生发展中的作用机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Li, Huimin, Guo, Jun, Jia, Yiting, Kong, Wei, Li, Wei. 2021. LOXL4 Abrogation Does Not Exaggerate Angiotensin II-Induced Thoracic or Abdominal Aortic Aneurysm in Mice. In Genes, 12, . doi:10.3390/genes12040513. https://pubmed.ncbi.nlm.nih.gov/33807332/
2. Tian, Mengxin, Liu, Weiren, Jin, Lei, Fan, Jia, Shi, Yinghong. 2015. LOXL4 is downregulated in hepatocellular carcinoma with a favorable prognosis. In International journal of clinical and experimental pathology, 8, 3892-900. doi:. https://pubmed.ncbi.nlm.nih.gov/26097573/
3. Li, Rongkun, Wang, Yahui, Zhang, Xiaoxin, Shang, Mingyi, Jiang, Shuheng. 2019. Exosome-mediated secretion of LOXL4 promotes hepatocellular carcinoma cell invasion and metastasis. In Molecular cancer, 18, 18. doi:10.1186/s12943-019-0948-8. https://pubmed.ncbi.nlm.nih.gov/30704479/
4. Deng, Hui, Lv, Lei, Li, Yang, He, Yinghua, Zhu, Jingde. 2014. miR-193a-3p regulates the multi-drug resistance of bladder cancer by targeting the LOXL4 gene and the oxidative stress pathway. In Molecular cancer, 13, 234. doi:10.1186/1476-4598-13-234. https://pubmed.ncbi.nlm.nih.gov/25311867/
5. Görögh, T, Weise, J B, Holtmeier, C, Ambrosch, P, Csiszar, K. . Selective upregulation and amplification of the lysyl oxidase like-4 (LOXL4) gene in head and neck squamous cell carcinoma. In The Journal of pathology, 212, 74-82. doi:. https://pubmed.ncbi.nlm.nih.gov/17354256/
6. Li, Rong-kun, Zhao, Wen-yi, Fang, Fang, Cao, Hui, Zhang, Zhi-gang. 2014. Lysyl oxidase-like 4 (LOXL4) promotes proliferation and metastasis of gastric cancer via FAK/Src pathway. In Journal of cancer research and clinical oncology, 141, 269-81. doi:10.1007/s00432-014-1823-z. https://pubmed.ncbi.nlm.nih.gov/25216702/
7. Vijayan, Poornima, Hack, Saidah, Yao, Tony, Pei, York, Barua, Moumita. 2021. LAMA2 and LOXL4 are candidate FSGS genes. In BMC nephrology, 22, 320. doi:10.1186/s12882-021-02524-6. https://pubmed.ncbi.nlm.nih.gov/34565340/
8. Choi, Sul Ki, Kim, Hoe Suk, Jin, Tiefeng, Moon, Woo Kyung. . LOXL4 knockdown enhances tumor growth and lung metastasis through collagen-dependent extracellular matrix changes in triple-negative breast cancer. In Oncotarget, 8, 11977-11989. doi:10.18632/oncotarget.14450. https://pubmed.ncbi.nlm.nih.gov/28060764/