SOCS proteins and their roles in the development of glioblastoma (Review)

Dai,Lirui; Li,Zian; Liang,Wulong; Hu,Weihua; Zhou,Shaolong; Yang,Zhuo; Tao,Yiran; Hou,Xuelei; Xing,Zhe; Mao,Jianchao; Shi,Zimin; Wang,Xinjun

doi:10.3892/ol.2021.13123

SOCS proteins and their roles in the development of glioblastoma (Review)

Authors:
- Lirui Dai
- Zian Li
- Wulong Liang
- Weihua Hu
- Shaolong Zhou
- Zhuo Yang
- Yiran Tao
- Xuelei Hou
- Zhe Xing
- Jianchao Mao
- Zimin Shi
- Xinjun Wang
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Affiliations: 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
Published online on: November 5, 2021 https://doi.org/10.3892/ol.2021.13123
Article Number: 5
Copyright: © Dai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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