Suppression of SOCS3 enhances TRAIL-induced cell growth inhibition through the upregulation of DR4 expression in renal cell carcinoma cells

Yabe, Michihiro; Ishibashi, Keiichiro; Onagi, Akifumi; Tanji, Ryo; Honda-Takinami, Ruriko; Koguchi, Tomoyuki; Matsuoka, Kanako; Hoshi, Seiji; Hata, Junya; Kataoka, Masao; Ogawa, Soichiro; Hiraki, Hiroyuki; Haga, Nobuhiro; Kojima, Yoshiyuki

doi:10.18632/oncotarget.25851

Cited by 9 publications

(7 citation statements)

References 49 publications

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“…However, survival prognostic analysis showed that abnormal SOCS3 expression was varied among the different tumors. For example, GBM patients with high expression of SOCS3 has a poorer OS, while KIRC patients exhibited the opposite result, and these results were consistent with previous in vivo and in vitro studies (13,42).…”

Section: Discussionsupporting

confidence: 90%

SOCS3 Acts as an Onco-immunological Biomarker With Value in Assessing the Tumor Microenvironment, Pathological Staging, Histological Subtypes, Therapeutic Effect, and Prognoses of Several Types of Cancer

et al. 2022

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The suppressor of cytokine signaling (SOCS) family contains eight members, including SOCS1–7 and CIS, and SOCS3 has been shown to inhibit cytokine signal transduction in various signaling pathways. Although several studies have currently shown the correlations between SOCS3 and several types of cancer, no pan-cancer analysis is available to date. We used various computational tools to explore the expression and pathogenic roles of SOCS3 in several types of cancer, assessing its potential role in the pathogenesis of cancer, in tumor immune infiltration, tumor progression, immune evasion, therapeutic response, and prognostic. The results showed that SOCS3 was downregulated in most The Cancer Genome Atlas (TCGA) cancer datasets but was highly expressed in brain tumors, breast cancer, esophageal cancer, colorectal cancer, and lymphoma. High SOCS3 expression in glioblastoma multiforme (GBM) and brain lower-grade glioma (LGG) were verified through immunohistochemical experiments. GEPIA and Kaplan–Meier Plotter were used, and this bioinformatics analysis showed that high SOCS3 expression was associated with a poor prognosis in the majority of cancers, including LGG and GBM. Our analysis also indicated that SOCS3 may be involved in tumor immune evasion via immune cell infiltration or T-cell exclusion across different types of cancer. In addition, SOCS3 methylation was negatively correlated with mRNA expression levels, worse prognoses, and dysfunctional T-cell phenotypes in various types of cancer. Next, different analytical methods were used to select genes related to SOCS3 gene alterations and carcinogenic characteristics, such as STAT3, SNAI1, NFKBIA, BCL10, TK1, PGS1, BIRC5, TMC8, and AFMID, and several biological functions were identified between them. We found that SOCS3 was involved in cancer development primarily through the JAK/STAT signaling pathway and cytokine receptor activity. Furthermore, SOCS3 expression levels were associated with immunotherapy or chemotherapy for numerous types of cancer. In conclusion, this study showed that SOCS3 is an immune-oncogenic molecule that may possess value as a biomarker for diagnosis, treatment, and prognosis of several types of cancer in the future.

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Section: Discussionsupporting

confidence: 90%

SOCS3 Acts as an Onco-immunological Biomarker With Value in Assessing the Tumor Microenvironment, Pathological Staging, Histological Subtypes, Therapeutic Effect, and Prognoses of Several Types of Cancer

et al. 2022

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“…The tumour immune microenvironment is associated with the therapeutic and prognostic response of tumours 36,37 . The current study revealed that SOCS1/2/3/4 expression was associated with immune cell infiltration in GBM.…”

Section: Discussionmentioning

confidence: 53%

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

Dai

Han

Yang

et al. 2023

J Cellular Molecular Medi

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Suppressor of cytokine signalling (SOCS) 1/2/3/4 are involved in the occurrence and progression of multiple malignancies; however, their prognostic and developmental value in patients with glioblastoma (GBM) remains unclear. The present study used TCGA, ONCOMINE, SangerBox3.0, UALCAN, TIMER2.0, GENEMANIA, TISDB, The Human Protein Atlas (HPA) and other databases to analyse the expression profile, clinical value and prognosis of SOCS1/2/3/4 in GBM, and to explore the potential development mechanism of action of SOCS1/2/3/4 in GBM. The majority of analyses showed that SOCS1/2/3/4 transcription and translation levels in GBM tissues were significantly higher than those in normal tissues. qRT‐PCR, western blotting (WB) and immunohistochemical staining were used to verify that SOCS3 was expressed at higher mRNA and protein levels in GBM than in normal tissues or cells. High SOCS1/2/3/4 mRNA expression was associated with poor prognosis in patients with GBM, especially SOCS3. SOCS1/2/3/4 were highly contraindicated, which had few mutations, and were not associated with clinical prognosis. Furthermore, SOCS1/2/3/4 were associated with the infiltration of specific immune cell types. In addition, SOCS3 may affect the prognosis of patients with GBM through JAK/STAT signalling pathway. Analysis of the GBM‐specific protein interaction (PPI) network showed that SOCS1/2/3/4 were involved in multiple potential carcinogenic mechanisms of GBM. In addition, colony formation, Transwell, wound healing and western blotting assays revealed that inhibition of SOCS3 decreased the proliferation, migration and invasion of GBM cells. In conclusion, the present study elucidated the expression profile and prognostic value of SOCS1/2/3/4 in GBM, which may provide potential prognostic biomarkers and therapeutic targets for GBM, especially SOCS3.

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“…Previous studies have revealed the functions of several SOCS family genes and JAK/STAT pathway in kidney cancer ( Horiguchi et al, 2002c ; Stofas et al, 2014 ; Wake and Watson, 2015 ; Yabe et al, 2018 ; Liang et al, 2020b ); however, whether the expression levels of SOCS can affect the prognosis of patients with KIRC is not fully understood. Recently, with the development of unique prediction techniques, it is possible to fully understand the role of SOCS family members.…”

Section: Introductionmentioning

confidence: 99%

Identification of the Prognostic Value Among Suppressor Of Cytokine Signaling Family Members in Kidney Renal Clear Cell Carcinoma

Zhang

Fang

et al. 2021

Front. Mol. Biosci.

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Background: Kidney renal clear cell carcinoma (KIRC) has become one of the most prevalent malignancies worldwide and remains a crucial cause of cancer-related morbidity and mortality. Aberrant activation of the JAK/STAT pathway acts as an important role in KIRC. The suppressor of cytokine signaling (SOCS) family members are the key negative regulators of the JAK/STAT pathway. SOCS family members have been verified to act as significant roles in regulating cellular responses to many cytokines and growth factors. However, whether the expression levels of SOCS affect the prognosis of patients with KIRC is still elusive.Methods: We first evaluated the expression of SOCS family genes in KIRC and determined the correlation between SOCS expression and different clinicopathological features. Then, we analyzed the genetic alterations, potential functions, transcription factor targets, and immune infiltration of SOCS family members based on the information available on public databases. Finally, we assessed the prognostic value of differentially expressed SOCS family members.Results: The expression levels of SOCS2, SOCS4, SOCS6, SOCS7, and CISH were downregulated in KIRC, and all SOCS genes were associated with clinicopathological features of patients with KIRC. SOCS family members have been predominantly related to protein binding, signaling adaptor activity, and JAK/STAT cascade. We found that STAT3, STAT6, and IRF1 are the key transcription factors that may be participated in the regulation of SOCS. We also found an association between the expression levels of SOCS and the immune infiltrates of KIRC. Finally, we have illuminated that SOCS1 and SOCS3 are risky genes, whereas SOCS2, SOCS4, SOCS6, SOCS7, and CISH are some of the protective genes for patients with KIRC; based on these, we have created a KIRC prognostic index for predicting the prognosis of patients of KIRC.Conclusion: Our study may contribute to further understanding the functions of SOCS genes in KIRC, which may help clinicians in selecting the appropriate drugs and predicting the outcomes for patients with KIRC.

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Suppression of SOCS3 enhances TRAIL-induced cell growth inhibition through the upregulation of DR4 expression in renal cell carcinoma cells

Cited by 9 publications

References 49 publications

SOCS3 Acts as an Onco-immunological Biomarker With Value in Assessing the Tumor Microenvironment, Pathological Staging, Histological Subtypes, Therapeutic Effect, and Prognoses of Several Types of Cancer

SOCS3 Acts as an Onco-immunological Biomarker With Value in Assessing the Tumor Microenvironment, Pathological Staging, Histological Subtypes, Therapeutic Effect, and Prognoses of Several Types of Cancer

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

Identification of the Prognostic Value Among Suppressor Of Cytokine Signaling Family Members in Kidney Renal Clear Cell Carcinoma

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