Dai Lirui, Li Zian, Liang Wulong, Hu Weihua, Zhou Shaolong, Yang Zhuo, Tao Yiran, Hou Xuelei, Xing Zhe, Mao Jianchao, Shi Zimin, Wang Xinjun
Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Department of Science and Technology of Henan Province, Henan International Joint Laboratory of Glioma Metabolism and Microenvironment Research, Zhengzhou, Henan 450052, P.R. China.
Oncol Lett. 2022 Jan;23(1):5. doi: 10.3892/ol.2021.13123. Epub 2021 Nov 5.
Glioblastoma multiforme (GBM) is the most common type of primary brain tumor in adults. GBM is characterized by a high degree of malignancy and aggressiveness, as well as high morbidity and mortality rates. GBM is currently treatable via surgical resection, chemotherapy and radiotherapy, but the prognosis of patients with GBM is poor. The suppressor of cytokine signaling (SOCS) protein family comprises eight members, including SOCS1-SOCS7 and cytokine-inducible SH2-containing protein. SOCS proteins regulate the biogenesis of GBM via the JAK/STAT and NF-κB signaling pathways. Driven by NF-κB, the expression of SOCS proteins can serve as a negative regulator of the JAK/STAT signaling pathway and exerts a potential inhibitory effect on GBM. In GBM, E3 ubiquitin ligase is involved in the regulation of cellular functions, such as the receptor tyrosine kinase (RTK) survival signal, in which SOCS proteins negatively regulate RTK signaling, and kinase overexpression or mutation can lead to the development of malignancies. Moreover, SOCS proteins affect the proliferation and differentiation of GBM cells by regulating the tumor microenvironment. SOCS proteins also serve specific roles in GBM of different grades and different isocitrate dehydrogenase mutation status. The aim of the present review was to describe the biogenesis and function of the SOCS protein family, the roles of SOCS proteins in the microenvironment of GBM, as well as the role of this protein family and E3 ubiquitin ligases in GBM. Furthermore, the role of SOCS proteins as diagnostic and prognostic markers in GBM and their potential role as GBM therapeutics were explored.
多形性胶质母细胞瘤（GBM）是成人中最常见的原发性脑肿瘤类型。GBM的特征是高度恶性和侵袭性，以及高发病率和死亡率。目前GBM可通过手术切除、化疗和放疗进行治疗，但GBM患者的预后较差。细胞因子信号转导抑制因子（SOCS）蛋白家族包括八个成员，即SOCS1 - SOCS7和细胞因子诱导含SH2蛋白。SOCS蛋白通过JAK/STAT和NF-κB信号通路调节GBM的发生。在NF-κB的驱动下，SOCS蛋白的表达可作为JAK/STAT信号通路的负调节因子，并对GBM发挥潜在的抑制作用。在GBM中，E3泛素连接酶参与细胞功能的调节，如受体酪氨酸激酶（RTK）存活信号，其中SOCS蛋白负调节RTK信号，激酶的过表达或突变可导致恶性肿瘤的发生。此外，SOCS蛋白通过调节肿瘤微环境影响GBM细胞的增殖和分化。SOCS蛋白在不同分级和不同异柠檬酸脱氢酶突变状态的GBM中也发挥特定作用。本综述的目的是描述SOCS蛋白家族的发生和功能、SOCS蛋白在GBM微环境中的作用，以及该蛋白家族和E3泛素连接酶在GBM中的作用。此外，还探讨了SOCS蛋白作为GBM诊断和预后标志物的作用及其作为GBM治疗药物的潜在作用。
