PDLIM4,也称为PDZ和LIM结构域蛋白4,是一种重要的适配蛋白。它包含PDZ结构域和LIM结构域,这两个结构域在蛋白质相互作用中起着关键作用。PDLIM4通过与多种蛋白质相互作用,参与细胞骨架重塑、细胞迁移、细胞分化和信号转导等生物学过程。PDLIM4在多种疾病中发挥重要作用,包括骨质疏松症、癌症和自身免疫性疾病。
在骨质疏松症中,PDLIM4基因多态性与骨折易感性相关。研究发现,PDLIM4基因中的某些单核苷酸多态性(SNPs)与骨质疏松性骨折的风险增加相关。例如,rs270611和rs3900945位点的A等位基因和C等位基因携带者分别表现出较高的骨折风险,而rs366512位点的T等位基因携带者则表现出对骨折的保护作用[1]。这些发现表明PDLIM4基因多态性可能影响骨密度和骨质量,从而影响骨质疏松症的发生和发展。
在癌症中,PDLIM4的表达与多种癌症的预后相关。研究发现,PDLIM4在急性髓系白血病(AML)中表达下调,并且与较好的预后相关[3]。PDLIM4的低表达在AML的某些亚型中更为常见,如M1/M2/M3型,并且与患者较长的总生存期相关。此外,PDLIM4的低表达与乳腺癌细胞的侵袭性和转移能力相关,提示PDLIM4可能作为乳腺癌治疗的潜在靶点[4]。PDLIM4的低表达还与卵巢癌患者的较差预后相关,并且通过抑制STAT3信号通路来抑制卵巢癌细胞的生长和侵袭[7]。此外,PDLIM4在胶质母细胞瘤、前列腺癌和甲状腺癌中也表现出与预后相关的表达模式[5,6,8]。
PDLIM4还与T细胞 trafficking有关。研究发现,PDLIM4与S1P1和肌动蛋白相互作用,从而调节T细胞的迁移和定位[2]。PDLIM4的低表达导致T细胞在胸腺中积聚,并在二级淋巴器官中减少,从而影响T细胞的免疫监视功能。
综上所述,PDLIM4是一种重要的适配蛋白,参与细胞骨架重塑、细胞迁移、细胞分化和信号转导等生物学过程。PDLIM4在骨质疏松症、癌症和自身免疫性疾病中发挥重要作用,并且与疾病的预后相关。进一步研究PDLIM4的生物学功能和调控机制,有助于深入理解相关疾病的发病机制,并为疾病的诊断、治疗和预防提供新的思路和策略。
参考文献:
1. Chen, Jihang, Hong, Zheping, Zhao, Chen, Bi, Qing, Qiu, Binsong. 2019. Associations between polymorphisms of the PDLIM4 gene and susceptibility to osteoporotic fracture in an elderly population of Han Chinese. In Bioscience reports, 39, . doi:10.1042/BSR20181505. https://pubmed.ncbi.nlm.nih.gov/30578378/
2. Fu, Chuntang, Li, Qingtian, Zou, Jia, Wang, Helen Y, Wang, Rong-Fu. 2019. JMJD3 regulates CD4 T cell trafficking by targeting actin cytoskeleton regulatory gene Pdlim4. In The Journal of clinical investigation, 129, 4745-4757. doi:10.1172/JCI128293. https://pubmed.ncbi.nlm.nih.gov/31393857/
3. Li, Yun, Qian, Jun, Lin, Jiang, Chen, Qin, Ma, Ji-Chun. . Reduced expression of PDLIM4 gene correlates with good prognosis in acute myeloid leukemia. In Zhongguo shi yan xue ye xue za zhi, 21, 1111-5. doi:10.7534/j.issn.1009-2137.2013.05.005. https://pubmed.ncbi.nlm.nih.gov/24156416/
4. Kravchenko, Dmitry Sergeevich, Ivanova, Anna Evgenyevna, Podshivalova, Elizaveta Sergeevna, Chumakov, Stepan Petrovich. 2020. PDLIM4/RIL-mediated regulation of Src and malignant properties of breast cancer cells. In Oncotarget, 11, 22-30. doi:10.18632/oncotarget.27410. https://pubmed.ncbi.nlm.nih.gov/32002121/
5. Lu, Chih-Hao, Wei, Sung-Tai, Liu, Jia-Jun, Yu, Chin-Sheng, Chang, Sunny Li-Yun. 2022. Recognition of a Novel Gene Signature for Human Glioblastoma. In International journal of molecular sciences, 23, . doi:10.3390/ijms23084157. https://pubmed.ncbi.nlm.nih.gov/35456975/
6. Vanaja, Donkena Krishna, Ballman, Karla V, Morlan, Bruce W, Tindall, Donald J, Young, Charles Y F. . PDLIM4 repression by hypermethylation as a potential biomarker for prostate cancer. In Clinical cancer research : an official journal of the American Association for Cancer Research, 12, 1128-36. doi:. https://pubmed.ncbi.nlm.nih.gov/16489065/
7. Jia, Yanyan, Shi, Huirong, Cao, Yuan, Li, Meijuan, Li, Xueru. 2019. PDZ and LIM domain protein 4 suppresses the growth and invasion of ovarian cancer cells via inactivation of STAT3 signaling. In Life sciences, 233, 116715. doi:10.1016/j.lfs.2019.116715. https://pubmed.ncbi.nlm.nih.gov/31376371/
8. Li, Hai, Sun, Dongnan, Jin, Kai, Wang, Xudong. 2025. Identification of Novel Gene Signature Predicting Lymph Node Metastasis in Papillary Thyroid Cancer via Bioinformatics Analysis and in vitro Validation. In International journal of general medicine, 18, 1463-1479. doi:10.2147/IJGM.S502480. https://pubmed.ncbi.nlm.nih.gov/40110574/