Low expression of IL-37 protein is correlated with high Oct4 protein expression in hepatocellular carcinoma

Guo, Hongsheng; P, Li; Su, Liudan; Wu, Kun-Lung; Huang, Kai‐Wen; Lai, Ruizhi; Xu, Jing; Sun, Dingbao; Li, Shuxian; Deng, Ziliang; Wang, Yan; Guo, Haina; Chen, Zhangquan; Wang, Sen

doi:10.1016/j.gene.2020.144445

Cited by 6 publications

(6 citation statements)

References 23 publications

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“…As a predominant type of primary liver cancer, hepatocellular carcinoma (HCC) mainly originates from liver injury and inflammation triggered by various risk factors, including hepatitis virus infection, obesity, chronic alcohol consumption, and exposure to aflatoxin. 1,2 Due to the high recurrence, early invasion and metastasis, the number of deaths attributed to HCC are the third highest among all cancers worldwide. 3,4 Currently, the molecular mechanisms underlying HCC have not been elucidated and clinical methods for early diagnosis and treatments are lacking.…”

Section: Introductionmentioning

confidence: 99%

<p>RNF128 Promotes Malignant Behaviors via EGFR/MEK/ERK Pathway in Hepatocellular Carcinoma</p>

Bai

Zhang

Peng

et al. 2020

OTT

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Background: The ubiquitin-proteasome system participates in the pathogenesis and progression of hepatocellular carcinoma (HCC). As an E3 ubiquitin ligase, RNF128 has been proved vital in carcinogenesis, whereas, little is known about the oncogenic mechanisms of RNF128 in HCC. Materials and Methods: Through tissue microarray from HCC patients, we analyzed RNF128 expression and its relationship with clinical outcomes in HCC. Western blot and quantitative realtime polymerase chain reaction (qRT-PCR) were performed to examine expression levels of RNF128 in HCC tissues and cell lines. Effects of RNF128 on HCC cellular biological functions and the potential mechanism were evaluated through knockdown and overexpression assays in vitro and in vivo methods. Results: RNF128 expression was found to be remarkably elevated in HCC tissues compared with adjacent normal tissues. Furthermore, the overexpression of RNF128 enhanced hepatoma cells proliferation, colony formation, migration, invasion, and apoptotic resistance both in vitro and in vivo. Mechanistically, RNF128 activated EGFR/MEK/ERK signaling pathway and the EGFR inhibitor, gefitinib partially reversed RNF128-enhanced proliferation, invasion, and migration in hepatoma cells. Conclusion: RNF128 promotes HCC progression by activating EGFR/MEK/ERK signaling pathway, which might function as a novel prognostic molecular signature with the potential to be a candidate therapeutic target for HCC patients.

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Section: Introductionmentioning

confidence: 99%

<p>RNF128 Promotes Malignant Behaviors via EGFR/MEK/ERK Pathway in Hepatocellular Carcinoma</p>

Bai

Zhang

Peng

et al. 2020

OTT

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“…Previous studies have revealed that Oct4 promoted HCC progression under the stimulation of IL-6 (112), and IL-37 could significantly downregulate the expression of IL-6 in the diseases. Together with the findings that Oct4 expression reduced in IL-37-transfected HCC HepG2 and MHCC97H cells, IL-37 was therefore believed to suppress HCC development through inhibiting IL-6/Oct4 pathway (113). Furthermore, IL-37 was reported to protect HCC cells against tumor progression by activating immunity in TME via regulating NK cells (15).…”

Section: Suppression Of Tumor Cells Migration Invasion and Metastasismentioning

confidence: 86%

Novel insights into IL-37: an anti-inflammatory cytokine with emerging roles in anti-cancer process

Gu,

Jin,

Gao

et al. 2023

Front. Immunol.

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Interleukin-37 (IL-37) is a newly discovered member of IL-1 family. The cytokine was proved to have extensive protective effects in infectious diseases, allergic diseases, metabolic diseases, autoimmune diseases and tumors since its discovery. IL-37 was mainly produced by immune and some non-immune cells in response to inflammatory stimulus. The IL-37 precursors can convert into the mature forms after caspase-1 cleavage and activation intracellularly, and then bind to Smad-3 and transfer to the nucleus to inhibit the production and functions of proinflammatory cytokines; extracellularly, IL-37 binds to cell surface receptors to form IL-37/IL-18Rα/IL-1R8 complex to exert immunosuppressive function via inhibiting/activating multiple signal pathways. In addition, IL-37 can attenuate the pro-inflammatory effect of IL-18 through directly or forming an IL-37/IL-18BP/IL-18Rβ complex. Therefore, IL-37 has the ability to suppress innate and acquired immunity of the host, and effectively control inflammatory stimulation, which was considered as a new hallmark of cancer. Specifically, it is concluded that IL-37 can inhibit the growth and migration of tumor cells, prohibit angiogenesis and mediate the immunoregulation in tumor microenvironment, so as to exert effective anti-tumor effects. Importantly, latest studies also showed that IL-37 may be a novel therapeutic target for cancer monitoring. In this review, we summarize the immunoregulation roles and mechanisms of IL-37 in anti-tumor process, and discuss its progress so far and potential as tumor immunotherapy.

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“… 134 By assessing the correlation between IL-37 and serum AFP in patients with HCC, the inhibition of IL-37 expression was found to be potentially related to an increase in AFP secretion in cancer cells; however, the expression of IL-37 in paracancerous tissues is unrelated to serum AFP. 135 HCC is difficult to diagnose owing to its strong concealment; therefore, the combination of AFP detection and cancerous IL-37 can improve the sensitivity and accuracy of HCC diagnosis and prognosis. 136 Thus, IL-37 may play an important role in the diagnosis and treatment of HCC.…”

Section: Conclusion and Prospectsmentioning

confidence: 99%

Research Progress on the Role and Mechanism of IL-37 in Liver Diseases

Jiang,

Zhou,

Liu

et al. 2023

Semin Liver Dis

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Cytokines are important components of the immune system that can predict or influence the development of liver diseases. IL-37, a new member of the IL-1 cytokine family, exerts potent anti-inflammatory and immunosuppressive effects inside and outside cells. IL-37 expression differs before and after liver lesions, suggesting that it is associated with liver disease; however, its mechanism of action remains unclear. This article mainly reviews the biological characteristics of IL-37, which inhibits hepatitis, liver injury and liver fibrosis by inhibiting inflammation, and inhibits the development of hepatocellular carcinoma (HCC) by regulating the immune microenvironment. Based on additional evidence, combining IL-37 with liver disease markers for diagnosis and treatment can achieve more significant effects, suggesting that IL-37 can be developed into a powerful tool for the clinical adjuvant treatment of liver diseases, especially HCC.

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Low expression of IL-37 protein is correlated with high Oct4 protein expression in hepatocellular carcinoma

Cited by 6 publications

References 23 publications

<p>RNF128 Promotes Malignant Behaviors via EGFR/MEK/ERK Pathway in Hepatocellular Carcinoma</p>

<p>RNF128 Promotes Malignant Behaviors via EGFR/MEK/ERK Pathway in Hepatocellular Carcinoma</p>

Novel insights into IL-37: an anti-inflammatory cytokine with emerging roles in anti-cancer process

Research Progress on the Role and Mechanism of IL-37 in Liver Diseases

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