Interleukin 37 Expression Inhibits STAT3 to Suppress the Proliferation and Invasion of Human Cervical Cancer Cells

Wang, Sen; An, Weifang; Yao, Yunhong; Chen, Renhuai; Zheng, Xiaoxuan; Yang, Wanyong; Zhao, Yi; Hu, Xinrong; Jiang, Enping; Bie, Yanhong; Chen, Zhangquan; Ouyang, Ping; Zhang, He; Xiong, Hui

doi:10.7150/jca.12266

Cited by 53 publications

(63 citation statements)

References 14 publications

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“…IL‐37 has been identified as a natural suppressor of innate inflammatory and immune responses 8, 12. Recent studies have indicated that IL‐37 plays a protective role in tumor progression in mouse fibrosarcoma,9 human lung cancer,14, 42 hepatocellular carcinoma,13 breast cancer,43 cervical cancer,44 and renal cell carcinoma 45. Zhang et al15 found that IL‐37 inhibits colon cancer progression via β‐catenin suppression and that a lack of IL‐37 is associated with poor survival.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of nomograms integrating IL‐37 expression, neutrophil level, and MMR status in patients with colorectal cancer

et al. 2018

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Interleukin (IL)‐37 and neutrophils are considered to be involved in human cancer, but their prognostic significance in colorectal cancer (CRC) has not been elucidated. The aim of this study was to evaluate the prognostic value of IL‐37 expression and neutrophil levels in CRC. We retrospectively analyzed IL‐37 expression, CD66b+ neutrophil levels, and mismatch repair (MMR) status in 337 paraffin‐embedded CRC specimens from the training cohort by immunohistochemistry. Their prognostic values were assessed using Kaplan‐Meier curves and multivariate Cox regression models. Moreover, several risk factors were used to form nomograms to evaluate survival, and the performance of the nomograms was assessed with respect to calibration, discrimination, and clinical usefulness. Further validation was performed in an independent cohort of 245 cases. Low IL‐37 expression and high CD66b+ neutrophil levels were significantly associated with diminished disease‐free survival (DFS) and overall survival (OS), and patients with MMR‐deficient CRC had better clinical outcomes. Furthermore, multivariate Cox analysis identified IL‐37, CD66b+ neutrophils, and MMR status as independent prognostic factors for DFS and OS. Two nomograms integrating the three markers with four clinicopathological risk factors were developed and validated for predicting DFS and OS with good calibration and discrimination (C‐index: training cohort, 0.798 (95% confidence interval:0.764‐0.832) and 0.828 (0.796‐0.860), respectively; validation cohort, 0.739 (0.696‐0.783) and 0.761 (0.715‐0.808), respectively). Decision curve analysis demonstrated that the nomograms were clinically useful. Intratumoral IL‐37, CD66b+ neutrophils, and MMR status were independent prognostic factors for CRC patients. Nomograms incorporating these biomarkers and clinicopathological features could be conveniently used to facilitate the individualized prediction of DFS and OS.

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Section: Discussionmentioning

confidence: 99%

Prognostic significance of nomograms integrating IL‐37 expression, neutrophil level, and MMR status in patients with colorectal cancer

et al. 2018

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“…After transfection with siSTAT3, CC cell proliferation and invasion inhibited by IL-37 was significantly reversed. STAT3 overexpression restored the CC cell growth and invasion, and increased the transcription of TNF-α and IL-1β (12). IL-37 expression is upregulated in breast carcinoma tissues, which indicates that this cytokine may have a role in tumor progression (9,81).…”

Section: Chronic Inflammatory and Autoimmune Disordersmentioning

confidence: 99%

“…Wang et al offered evidence that IL-37 inhibits the proliferation and invasion of cervical cancer (CC) cells via the signal transducer and activator of transcription 3 (STAT3) signaling pathway (12). IL-37 upregulated STAT3 expression at the gene and protein levels and reduced STAT3 phosphorylation (12). After transfection with siSTAT3, CC cell proliferation and invasion inhibited by IL-37 was significantly reversed.…”

Section: Chronic Inflammatory and Autoimmune Disordersmentioning

confidence: 99%

“…The expression level of IL-37 is negatively correlated with tumor size and high IL-37 expression is linked to disease-free survival (DFS) and better overall survival (OS) in HCC patients, which suggests that IL-37 may be a potentially valuable prognostic marker for HCC patients (64). Wang et al offered evidence that IL-37 inhibits the proliferation and invasion of cervical cancer (CC) cells via the signal transducer and activator of transcription 3 (STAT3) signaling pathway (12). IL-37 upregulated STAT3 expression at the gene and protein levels and reduced STAT3 phosphorylation (12).…”

Section: Chronic Inflammatory and Autoimmune Disordersmentioning

confidence: 99%

“…The IL-37 gene seems to be absent in mice as no cDNA or genomic sequence related to human IL-37 has been reported (9,11). The IL-37 gene size is 3.617 kb and includes six exons which encode a 17-26 KDa protein (9,12). The IL-37 gene undergoes alternative splicing; five different splice variants of IL-37 have been identified and termed IL-37a-e, of which IL-37b is the largest (218 amino acids ) and best characterized isoform ( Fig.…”

Section: Location and Structure Of Il-37mentioning

confidence: 99%

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Interleukin-37: A crucial cytokine with multiple roles in disease and potentially clinical therapy (Review)

et al. 2018

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Abstract. Interleukin (IL)-37, a new IL-1 family member, has received increasing attention in recent years. In the past decade, it has been determined that IL-37 is expressed in various normal cells and tissues and is regulated by inflammatory stimuli and pro-cytokines via different signal transduction pathways. Recently, it has been found that IL-37 is expressed in a variety of cancers, chronic inflammatory and autoimmune disorders, and exerts anti-inflammatory effects. Moreover, a growing body of literature demonstrates that IL-37 plays a vital role in inhibiting both innate and adaptive immune responses as well as inflammatory reactions. In addition, IL-37 may prove to be a new and potentially useful target for effective cytokine therapy. Further evidence is needed to clarify in more detail the effects of IL-37 in experimental and clinical studies. Based on an extensive summary of published data, the aim of this review is to outline the current knowledge of IL-37, including the location, structure, expression, regulation and function, as well as the potential clinical applications of this cytokine.

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Cervical cancer stem‐like cells: systematic review and identification of reference genes for gene expression

Campos

Schultz

Mello

et al. 2017

Cell Biology International

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Cervical cancer is the fourth most common cancer affecting women worldwide. Among many factors, the presence of cancer stem cells, a subpopulation of cells inside the tumor, has been associated with a worse prognosis. Considering the importance of gene expression studies to understand the biology of cervical cancer stem cells (CCSC), this work identifies stable reference genes for cervical cancer cell lines SiHa, HeLa, and ME180 as well as their respective cancer stem-like cells. A literature review was performed to identify validated reference genes currently used to normalize RT-qPCR data in cervical cancer cell lines. Then, cell lines were cultured in regular monolayer or in a condition that favors tumor sphere formation. RT-qPCR was performed using five reference genes: ACTB, B2M, GAPDH, HPRT1, and TBP. Stability was assessed to validate the selected genes as suitable reference genes. The evaluation validated B2M, GAPDH, HPRT1, and TBP in these experimental conditions. Among them, GAPDH and TBP presented the lowest variability according to the analysis by Normfinder, Bestkeeper, and ΔC methods, being therefore the most adequate genes to normalize the combination of all samples. These results suggest that B2M, GAPDH, HPRT1, and TBP are suitable reference genes to normalize RT-qPCR data of established cervical cancer cell lines SiHa, HeLa, and ME180 as well as their derived cancer stem-like cells. Indeed, GAPDH and TBP seem to be the most convenient choices for studying gene expression in these cells in monolayers or spheres.

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Interleukin 37 Expression Inhibits STAT3 to Suppress the Proliferation and Invasion of Human Cervical Cancer Cells

Cited by 53 publications

References 14 publications

Prognostic significance of nomograms integrating IL‐37 expression, neutrophil level, and MMR status in patients with colorectal cancer

Prognostic significance of nomograms integrating IL‐37 expression, neutrophil level, and MMR status in patients with colorectal cancer

Interleukin-37: A crucial cytokine with multiple roles in disease and potentially clinical therapy (Review)

Cervical cancer stem‐like cells: systematic review and identification of reference genes for gene expression

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