ACTN4,也称为α-actinin-4,是一种编码非肌肉型α-actinin蛋白的基因。α-actinin是一类与肌动蛋白结合的蛋白质,它们在细胞骨架的组装和调节中发挥重要作用。α-actinin-4主要存在于细胞质中,参与细胞骨架的重塑、细胞粘附、迁移以及信号传导等多种细胞过程。ACTN4的表达异常与多种疾病的发生发展密切相关,包括癌症、肾脏疾病以及妊娠相关的高血压等。
ACTN4基因的异常表达和突变已被证明与多种癌症的发生和进展有关。例如,研究发现,ACTN4基因的扩增与非小细胞肺癌(NSCLC)的复发和转移能力相关。在NSCLC患者中,ACTN4基因的扩增与对辅助化疗的敏感性相关,可以作为预测患者预后的生物标志物[1,3]。此外,ACTN4基因的扩增也与口腔舌癌的预后相关,ACTN4基因扩增的患者生存期显著缩短[6]。
在肾脏疾病方面,ACTN4基因的突变与家族性局灶节段性肾小球硬化症(FSGS)的发生相关。FSGS是原发性肾病综合征(PNS)的一种常见原因。研究发现,ACTN4基因的突变会导致肾脏滤过屏障的破坏,从而引发肾脏功能障碍[2,7]。此外,ACTN4基因的表达异常还与妊娠相关的高血压,如子痫前期等疾病的发生相关[4]。
除了在癌症和肾脏疾病中的作用外,ACTN4基因还与细胞死亡相关。研究发现,ACTN4基因的表达与肺癌的细胞死亡相关,可以作为肺癌的诊断和治疗的新靶点[5]。
综上所述,ACTN4基因在多种疾病的发生发展中发挥重要作用。其异常表达和突变与癌症、肾脏疾病以及妊娠相关的高血压等疾病的发生发展密切相关。因此,深入研究ACTN4基因的功能和调控机制,对于理解相关疾病的发病机制、寻找新的诊断和治疗方法具有重要意义。
参考文献:
1. Tozuka, Takehiro, Noro, Rintaro, Seike, Masahiro, Honda, Kazufumi. 2022. Benefits from Adjuvant Chemotherapy in Patients with Resected Non-Small Cell Lung Cancer: Possibility of Stratification by Gene Amplification of ACTN4 According to Evaluation of Metastatic Ability. In Cancers, 14, . doi:10.3390/cancers14184363. https://pubmed.ncbi.nlm.nih.gov/36139525/
2. Meng, Lingzhang, Cao, Shan, Lin, Na, Wang, Jie, Liu, Yunguang. 2019. Identification of a Novel ACTN4 Gene Mutation Which Is Resistant to Primary Nephrotic Syndrome Therapy. In BioMed research international, 2019, 5949485. doi:10.1155/2019/5949485. https://pubmed.ncbi.nlm.nih.gov/31930129/
3. Noro, Rintaro, Honda, Kazufumi, Nagashima, Kengo, Gemma, Akihiko, Kubota, Kaoru. 2022. Alpha-actinin-4 (ACTN4) gene amplification is a predictive biomarker for adjuvant chemotherapy with tegafur/uracil in stage I lung adenocarcinomas. In Cancer science, 113, 1002-1009. doi:10.1111/cas.15228. https://pubmed.ncbi.nlm.nih.gov/34845792/
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5. Xie, Kai, Wang, Bin, Pang, Pei, Feng, Yu, Ma, Haitao. 2024. A novel disulfidptosis-related prognostic gene signature and experimental validation identify ACTN4 as a novel therapeutic target in lung adenocarcinoma. In Cancer biomarkers : section A of Disease markers, , . doi:10.3233/CBM-230276. https://pubmed.ncbi.nlm.nih.gov/38517776/
6. Kakuya, T, Mori, T, Yoshimoto, S, Shibahara, T, Honda, K. 2017. Prognostic significance of gene amplification of ACTN4 in stage I and II oral tongue cancer. In International journal of oral and maxillofacial surgery, 46, 968-976. doi:10.1016/j.ijom.2017.03.001. https://pubmed.ncbi.nlm.nih.gov/28385383/
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