FAT10在胶质瘤发生发展和放疗抵抗中的可能作用机制  

The contribution and mechanism of FAT10 involved in the tumorigenesis and radioresistance of glioma

作　　者：刘辉[1] 闵彬[2] 涂艳阳[1] LIU Hui;MIN Bin;TU Yan-Yang(Department of Experimental Surgery,Tangdu Hospital,Fourth Military Medical University,Xi an,710038,China;Out patient Department of Air Force Engineering University,Xi an 710051,China)

机构地区：[1]第四军医大学唐都医院实验外科,陕西西安710038 [2]空军工程大学门诊部,陕西西安710051

出　　处：《转化医学电子杂志》2018年第1期6-11,共6页E-Journal of Translational Medicine

基　　金：国家自然科学基金(81572983;81702458);陕西省社会发展科技攻关项目(2015SF-627)

摘　　要：恶性胶质瘤是中枢神经系统常见的原发性肿瘤,即便最大程度地切除肿瘤后联合进行放化疗,其预后仍然很差。其中一个重要原因是胶质瘤细胞对放疗产生抵抗。FAT10作为与泛素在结构和功能最相似的一个泛素样调节子(UBL)蛋白,在肿瘤的发生发展及放疗抵抗中扮演了重要角色,但其在恶性胶质瘤中的活性及功能却鲜有报道。我们前期的研究指出,FAT10随着胶质瘤级别的升高而表达增强,并在胶质瘤细胞系中高表达;且有研究也证实,FAT10参与调控肿瘤的发生发展,且其可以对PI3K/GSK3β/Cyclin D1通路进行调控,而这种调控很可能在胶质瘤的发生发展及放疗抵抗过程中发挥重要作用。因此,本文将探讨FAT10介导的PI3K/Akt/GSK3β/Cyclin D1通路在胶质瘤发生发展中的可能作用,并从G1/S期转变、DNA损伤反应和DNA双链断裂三个方面探索FAT10影响胶质瘤放疗抵抗的分子机制,为胶质瘤的临床治疗提供新的靶标。Malignant glioma is a common primary tumor in the central nervons system,the prognosis of which remain very poor even after the maximum excision combined with radiotheragy and chemotherapy.As an ubiquitin-like protein with the similar structure and function of ubiquitin,FAT10 plays a significant role in the tumorigenesis and radioresistance of glioma.However,only a few of studies about FAT10 activity and function in glioma were reported.According to our previous studies,FAT10 was highly expressed in the glioma cell lines and it even increased accompanied by the malignant grade of glioma.Furthermore,it was proved that FAT10 regulated the progression of tumorigenesis through PI3K/GSK3β/CyclinD1 signal pathway,the same as the radioresistance of glioma.As a result,our study aims to reveal the influence of FAT10 regulating the tumorigenesis and radioresistance of glioma through the PI3K/Akt/GSK3β/CyclinD1 signal pathway.Moreover,we will also explore the molecular mechanism of FAT10 on the radioresistance of glioma through the aspects of G1/S phase transition,DNA damage response and DNA double-strand breaks to provide a novel therapeutic target for glioma.

关 键 词：胶质瘤 肿瘤发生 放疗抵抗性 FAT10 PI3K/Akt/GSK3β/CyclinD1通路 

分 类 号：R739.41[医药卫生—肿瘤]