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

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.

Ciliary Neurotrophic Factor Derived From Astrocytes Protects Retinal Ganglion Cells Through PI3K/AKT, JAK/STAT, and MAPK/ERK Pathways

“…One of the upregulated genes, SOCS3 , has been reported to be associated with the proliferation of neural tissue. 57 Expression of clusterin, a stress-related gene that promotes cell survival, 58 was also increased. Additionally, several upregulated genes, such as shisa5 and BCL3 , were identified, and their biological processes were reported but their relationships with RGCs were not.…”

Identification and validation of SOCS1/2/3/4 as potential prognostic biomarkers and correlate with immune infiltration in glioblastoma

“…As aforementioned above, siRNA was used for transfection and Western blotting was performed to verify the knockdown efficiency. Numerous studies have revealed that SOCS3 expression is closely associated with the proliferation of tumour cells 33,34 . The current study used SOCS3 as a marker of cell proliferation for knockdown experiments, and detected PCNA expression by Western blotting, which revealed that the expression level of PCNA was reduced (Figure 12A).…”

“…It has also been found that EYA2 is downregulated in hepatocellular carcinoma (HCC), and EYA2 can regulate SOCS3 expression in combination with DACH1 transcription, thereby inhibiting HCC progression via SOCS3 ‐mediated blockade of the JAK/STAT signalling pathway 44 . Current studies have found that the high expression of SOCS3 can promote the proliferation of GBM cells 34 . Therefore, we want to further study the other functions of SOCS3 , including migration and invasion, and explore the potential mechanisms of SOCS3 's possible regulatory role by bioinformatics analysis, so as to prepare for further exploration of SOCS3 mechanisms in GBM in the future.…”

Overexpression of prothymosin-α in glioma is associated with tumor aggressiveness and poor prognosis

“…The recent emergence of high throughput sequencing and proteomics analysis has enhanced the understanding of glioma biology and also aided in the identification of novel biomarkers [ 55 ]. Numerous studies have utilized gene expression datasets from TCGA, CGGA etc., to identify potential prognostic biomarkers in glioma such as GINS4 [ 56 ], SOCS3 [ 57 ], PTPRN [ 58 ], PLAT, IGFBP2, BCAT1, SERPINH1 [ 59 ], MAGEH1 [ 55 ] etc. Some of these markers have also been validated further in the patient cohort and also by functional analysis [ 56 , 57 ].…”

“…Numerous studies have utilized gene expression datasets from TCGA, CGGA etc., to identify potential prognostic biomarkers in glioma such as GINS4 [ 56 ], SOCS3 [ 57 ], PTPRN [ 58 ], PLAT, IGFBP2, BCAT1, SERPINH1 [ 59 ], MAGEH1 [ 55 ] etc. Some of these markers have also been validated further in the patient cohort and also by functional analysis [ 56 , 57 ]. The same datasets have been used in the present study to establish the utility of PTMA as an independent predictor of patient survival.…”