Osgin2,即氧化应激诱导的生长抑制剂家族成员2,是一种在多种生物学过程中发挥重要作用的基因。Osgin2的表达与氧化应激、细胞周期、细胞自噬、肿瘤免疫浸润等多种生物学过程相关,其在肿瘤发生、发展、预后和治疗中具有潜在的应用价值。
在胃癌中,Osgin2表达水平与患者预后相关。研究发现,胃癌细胞和组织中Osgin2水平较高,与胃癌患者不良预后相关[1]。Osgin2在细胞周期、自噬等生物学过程中发挥重要作用,与多种肿瘤相关信号通路相关。通过siRNA转染技术敲低Osgin2表达,可以抑制肿瘤细胞增殖,促进细胞周期阻滞,并影响肿瘤免疫浸润细胞,从而影响抗肿瘤免疫功能。这表明Osgin2作为新的生物标志物,在胃癌中具有诊断和预后价值,是潜在的胃癌治疗靶点[1]。
除了在胃癌中的研究,Osgin2在动脉粥样硬化中也发挥重要作用。研究发现,Nrf2-OSGIN1&2-HSP70轴介导了烟草烟雾诱导的内皮细胞脱落,与斑块侵蚀相关[2]。烟草烟雾提取物和肿瘤坏死因子-α(TNFα)可以增加Osgin1和Osgin2的表达,而敲低Osgin1&2可以抑制Nrf2诱导的细胞脱落。这表明Osgin2在动脉粥样硬化中可能发挥重要作用,是潜在的斑块侵蚀治疗靶点[2]。
此外,Osgin2在软组织肉瘤中也发挥重要作用。研究发现,低表达的miR-199a-5p与软组织肉瘤患者不良预后相关,而Osgin2基因的3'非编码区受miR-199a-5p的调控[3]。这表明Osgin2在软组织肉瘤中发挥重要作用,是潜在的软组织肉瘤治疗靶点[3]。
除了上述研究,Osgin2在肾脏损伤、神经毒性、冷适应等方面也发挥重要作用。研究发现,Tim-3缺陷可以通过调节NF-κB信号通路和线粒体损伤加重镉诱导的肾脏毒性[4]。银纳米颗粒(Ag-NPs)可以诱导神经元凋亡、线粒体损伤和MT3/OSGIN2表达改变[5]。在冷适应方面,Osgin2是鸡品种冷适应的候选基因之一[6]。此外,Osgin2在结直肠癌中也具有预后价值,是结直肠癌治疗潜在的药物靶点[7]。
综上所述,Osgin2是一种重要的基因,在多种生物学过程中发挥重要作用,包括氧化应激、细胞周期、细胞自噬、肿瘤免疫浸润、动脉粥样硬化、肾脏损伤、神经毒性、冷适应等。Osgin2在肿瘤发生、发展、预后和治疗中具有潜在的应用价值,是潜在的肿瘤治疗靶点。进一步研究Osgin2的生物学功能和作用机制,有助于深入理解肿瘤发生、发展的分子机制,为肿瘤的治疗和预防提供新的思路和策略。
参考文献:
1. Wang, Peipei, Zhu, Ying, Jia, Xinru, Sun, Leitao, Ruan, Shanming. 2023. Clinical prognostic value of OSGIN2 in gastric cancer and its proliferative effect in vitro. In Scientific reports, 13, 5775. doi:10.1038/s41598-023-32934-5. https://pubmed.ncbi.nlm.nih.gov/37031243/
2. Satta, Sandro, Beal, Robert, Smith, Rhys, Newby, Andrew C, White, Stephen J. . A Nrf2-OSGIN1&2-HSP70 axis mediates cigarette smoke-induced endothelial detachment: implications for plaque erosion. In Cardiovascular research, 119, 1869-1882. doi:10.1093/cvr/cvad022. https://pubmed.ncbi.nlm.nih.gov/36804807/
3. Keßler, Jacqueline, Rot, Swetlana, Bache, Matthias, Taubert, Helge, Greither, Thomas. 2016. miR-199a-5p regulates HIF-1α and OSGIN2 and its expression is correlated to soft-tissue sarcoma patients' outcome. In Oncology letters, 12, 5281-5288. doi:10.3892/ol.2016.5320. https://pubmed.ncbi.nlm.nih.gov/28101243/
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5. Bonaventura, Gabriele, La Cognata, Valentina, Iemmolo, Rosario, D'Agata, Velia, Cavallaro, Sebastiano. 2018. Ag-NPs induce apoptosis, mitochondrial damages and MT3/OSGIN2 expression changes in an in vitro model of human dental-pulp-stem-cells-derived neurons. In Neurotoxicology, 67, 84-93. doi:10.1016/j.neuro.2018.04.014. https://pubmed.ncbi.nlm.nih.gov/29698629/
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