SOCS3 is Related to Cell Proliferation in Neuronal Tissue: An Integrated Analysis of Bioinformatics and Experiments

Yeuni Yu; Soon Ki Sung; Chi Hyung Lee; Mihyang Ha; Junho Kang; Eun Jung Kwon; Ji Wan Kang; Youngjoo Kim; Ga Hyun Kim; Hye Jin Heo; Hansong Lee; Tae Woo Kim; Yoonsung Lee; Kyungjae Myung; Chang-Kyu Oh; Yun Hak Kim

doi:10.3389/fgene.2021.743786

SOCS3 is Related to Cell Proliferation in Neuronal Tissue: An Integrated Analysis of Bioinformatics and Experiments

Front Genet. 2021 Sep 27:12:743786. doi: 10.3389/fgene.2021.743786. eCollection 2021.

Authors

Yeuni Yu¹, Soon Ki Sung², Chi Hyung Lee², Mihyang Ha³, Junho Kang¹, Eun Jung Kwon³, Ji Wan Kang³, Youngjoo Kim³, Ga Hyun Kim³, Hye Jin Heo⁴, Hansong Lee¹, Tae Woo Kim⁵, Yoonsung Lee^{6

7}, Kyungjae Myung⁶, Chang-Kyu Oh^{6

8}, Yun Hak Kim^{1

4}

Affiliations

¹ Department of Biomedical Informatics, School of Medicine, Pusan National University, Busan, South Korea.
² Department of Neurosurgery, Pusan National University Yangsan Hospital, Yangsan, South Korea.
³ Interdisciplinary Program of Genomic Science, Pusan National University, Yangsan, South Korea.
⁴ Department of Anatomy, School of Medicine, Pusan National University, Yangsan, South Korea.
⁵ Department of Orthopaedic Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea.
⁶ Center for Genomic Integrity, Institute for Basic Science (IBS), Ulsan, South Korea.
⁷ Department of Core Research Laboratory, Clinical Research Institute, Kyung Hee University Hospital at Gangdong, Seoul, South Korea.
⁸ Department of Anatomy, College of Medicine, Inje University, Busan, South Korea.

Abstract

Glioma is the most common primary malignant tumor that occurs in the central nervous system. Gliomas are subdivided according to a combination of microscopic morphological, molecular, and genetic factors. Glioblastoma (GBM) is the most aggressive malignant tumor; however, efficient therapies or specific target molecules for GBM have not been developed. We accessed RNA-seq and clinical data from The Cancer Genome Atlas, the Chinese Glioma Genome Atlas, and the GSE16011 dataset, and identified differentially expressed genes (DEGs) that were common to both GBM and lower-grade glioma (LGG) in three independent cohorts. The biological functions of common DEGs were examined using NetworkAnalyst. To evaluate the prognostic performance of common DEGs, we performed Kaplan-Meier and Cox regression analyses. We investigated the function of SOCS3 in the central nervous system using three GBM cell lines as well as zebrafish embryos. There were 168 upregulated genes and 50 downregulated genes that were commom to both GBM and LGG. Through survival analyses, we found that SOCS3 was the only prognostic gene in all cohorts. Inhibition of SOCS3 using siRNA decreased the proliferation of GBM cell lines. We also found that the zebrafish ortholog, socs3b, was associated with brain development through the regulation of cell proliferation in neuronal tissue. While additional mechanistic studies are necessary, our results suggest that SOCS3 is an important biomarker for glioma and that SOCS3 is related to the proliferation of neuronal tissue.

Keywords: GBM; SOCS3; development; proliferation; zebrafish.