Overexpression of SOCS3 mediated by adenovirus vector in mouse and human castration-resistant prostate cancer cells increases the sensitivity to NK cells in vitro and in vivo

Yoneda, Tomomi; Kunimura, Naoto; Kitagawa, Koichi; Fukui, Yuka; Saito, Hiroki; Narikiyo, Keita; Ishiko, Motoki; Otsuki, Naoki; Nibu, Ken‐ichi; Fujisawa, Masato; Serada, Satoshi; Naka, Tetsuji; Shirakawa, Toshiro

doi:10.1038/s41417-018-0075-5

Cited by 22 publications

(27 citation statements)

References 39 publications

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“…In addition, it has been observed that SOCS3 is inhibited in PCa, which leads to overactivation of the JAK/STAT3 signaling pathway [62]. Our research supports the function of the SOCS3/JAK2/STAT3 signaling axis in the PCa progression.…”

Section: Discussionsupporting

confidence: 82%

LINC00893 Inhibits The Progression of Prostate Cancer Through miR-3173-5p/SOCS3/JAK2/STAT3 Pathway

Yu¹,

Fan²,

Liu³

et al. 2021

Preprint

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Background: Prostate cancer (PCa) is one of the most common malignant tumors in the male urinary system. In recent years, the morbidity and mortality of PCa have been increasing due to the limited effects of existing treatment strategies. Long non-coding RNA (lncRNA) LINC00893 inhibits the proliferation and metastasis of papillary thyroid cancer (PTC) cells, but its role in PCa has not been reported. Our study aims to clarify the role and underlying mechanism of LINC00893 in regulating the progression of PCa.Methods: We analyzed LINC00893 expression through TCGA database. We also collected 66 paires of PCa tissues and matched para-cancerous tissues as well as cell lines and assessed LINC00893 expression. Subsequently, we conducted gain-of-function assays to confirm the role of LINC00893 in PCa. CCK-8, EdU, colony information and transwell assays were implemented to detect cell proliferation, colony formation and metastasis abilities, respectively. RT-qPCR and western blot assays were used to quantify the expression of mRNA and protein. Dual-luciferase reporter, RNA-binding protein immunoprecipitation (RIP) and RNA pull down assays were conducted to evaluate the interaction of molecules. Spearman correlation coefficient analysis was conducted to detect the correlation between molecules.Results: We found that the LINC00893 expression in PCa tissues and cell lines was upregulated compared with matched controls, and patients with low expression of LINC00893 suffered a low overall survival rate. Overexpression of LINC00893 hindered the proliferation, epithelial-mesenchymal transition (EMT) as well as metastasis of PCa cells in vitro and in vivo. In terms of mechanism, suppressor of cytokine signaling 3 (SOCS3)/Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway occupied a central position in the regulation of PCa progression by LINC00893. LINC00893 weakened the inhibition role of miR-3173-5p on SOCS3 expression through functioning as a miR-3173-5p sponge, which inhibited the JAK2/STAT3 signaling pathway. Conclusions: LINC00893 suppresses the progression of prostate cancer through miR-3173-5p/SOCS3/JAK2/STAT3 pathway. our data uncovers a novel mechanism by which LINC00893 hinders the progression of PCa, which enriches the molecular network of LINC00893 regulating the PCa progression and laies a theoretical foundation for PCa targeted therapy.

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Section: Discussionsupporting

confidence: 82%

LINC00893 Inhibits The Progression of Prostate Cancer Through miR-3173-5p/SOCS3/JAK2/STAT3 Pathway

Yu¹,

Fan²,

Liu³

et al. 2021

Preprint

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“…Recently, a series of studies have demonstrated that SOCS3 can also participate in the immune response by inhibiting the expression of inflammation-related cytokines [19,29,30]. It is striking that overexpression of SOCS3 strongly inhibited STAT1 phosphorylation and PD-L1 up-regulation, and further studies confirmed that SOCS3 regulates JAK/STAT3 pathway through immunoregulation [19,31]. As our results suggested that PD-L1 and SOCS3 are negatively correlated in HCC tissues, and it still remains ambiguous whether SOCS3 can selectively down-regulate PD-L1 to promote anti-cancer immune responses in HCC.…”

Section: Discussionmentioning

confidence: 94%

Correlation of PD-L1 and SOCS3 Co-expression with the Prognosis of Hepatocellular Carcinoma Patients

Chen¹,

Huang²,

Zhang³

et al. 2020

J. Cancer

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Purpose: To investigate the correlation between the expression of PD-L1, SOCS3 and immune-related biomarkers CD276, CD4, CD8 in hepatocellular carcinoma (HCC) and further determine the relationship with clinicopathologic characteristics and the prognostic value of their co-expression in HCC patients. Methods: We assessed the expression of PD-L1, CD276, SOCS3, CD4 and CD8 by immunohistochemistry in tumor tissue from 74 HCC patients who underwent curative hepatectomy. Results: High expression of PD-L1 was significantly associated with high Edmondson grade (p<0.01) and elevated enzyme (p=0.037); high expression of CD276 was significantly correlated with high Edmondson grade (p=0.021); high expression of SOCS3 was significantly associated with age (p=0.026) and tumor size (p=0.041), while PD-L1 showed no significant correlation. The expression of PD-L1, CD276, SOCS3 protein and other clinicopathological factors (sex, vascular invasion, tumor number, tumor capsule, pT stage, liver cirrhosis, HBsAg, TBiL, AFP) showed no significant correlation (p>0.05). High expression of CD8 was respectively significantly associated with worse overall survival (OS) (p=0.002). There was no significantly difference between CD4 and CD8 high-expression and overall survival (OS) (p=0.100). Both high expression of PD-L1 (p=0.003) and low expression of SOCS3 (p=0.015) was significantly associated with worse overall survival (OS). But CD276 only had a trendency (p=0.166). Additionally, multivariate Cox regression models implied that PD-L1, SOCS3, as well as both CD4 and CD8 was an independent prognostic factor for OS (p<0.05). Furthermore, HCC patients with PD-L1 low-expression and SOCS3 high-expression had a better prognostic according to the different pT stages (p<0.05). Conclusions: We for the first time demonstrated that PD-L1 and SOCS3 were independent prognostic factor for HCC patients. Co-expression of low PD-L1 and high SOCS3 could be a better predictive marker for HCC patients.

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“…Indeed, in liver cancer SOCS3 gene expression can be re-established by drugs that activate the Farnesoid X receptor (FXR) [163,164]. Gene therapy strategies are also under development to re-express SOCS1 or SOCS3 in tumors [165,166,167].…”

Section: Tumor Suppressor Functions and Negative Regulation Of Stamentioning

confidence: 99%

STAT3 and STAT5 Activation in Solid Cancers

Igelmann

Neubauer

Ferbeyre

2019

Cancers

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The Signal Transducer and Activator of Transcription (STAT)3 and 5 proteins are activated by many cytokine receptors to regulate specific gene expression and mitochondrial functions. Their role in cancer is largely context-dependent as they can both act as oncogenes and tumor suppressors. We review here the role of STAT3/5 activation in solid cancers and summarize their association with survival in cancer patients. The molecular mechanisms that underpin the oncogenic activity of STAT3/5 signaling include the regulation of genes that control cell cycle and cell death. However, recent advances also highlight the critical role of STAT3/5 target genes mediating inflammation and stemness. In addition, STAT3 mitochondrial functions are required for transformation. On the other hand, several tumor suppressor pathways act on or are activated by STAT3/5 signaling, including tyrosine phosphatases, the sumo ligase Protein Inhibitor of Activated STAT3 (PIAS3), the E3 ubiquitin ligase TATA Element Modulatory Factor/Androgen Receptor-Coactivator of 160 kDa (TMF/ARA160), the miRNAs miR-124 and miR-1181, the Protein of alternative reading frame 19 (p19ARF)/p53 pathway and the Suppressor of Cytokine Signaling 1 and 3 (SOCS1/3) proteins. Cancer mutations and epigenetic alterations may alter the balance between pro-oncogenic and tumor suppressor activities associated with STAT3/5 signaling, explaining their context-dependent association with tumor progression both in human cancers and animal models.

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Overexpression of SOCS3 mediated by adenovirus vector in mouse and human castration-resistant prostate cancer cells increases the sensitivity to NK cells in vitro and in vivo

Abstract: Yoneda, et al. 1 Overexpression of SOCS3 mediated by adenovirus vector in mouse and human castration resistant prostate cancer cells increases the sensitivity to NK cells in vitro and in vivo.

Cited by 22 publications

References 39 publications

LINC00893 Inhibits The Progression of Prostate Cancer Through miR-3173-5p/SOCS3/JAK2/STAT3 Pathway

LINC00893 Inhibits The Progression of Prostate Cancer Through miR-3173-5p/SOCS3/JAK2/STAT3 Pathway

Correlation of PD-L1 and SOCS3 Co-expression with the Prognosis of Hepatocellular Carcinoma Patients

STAT3 and STAT5 Activation in Solid Cancers

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