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http://hdl.handle.net/10553/119577
Title: | SOCS2 protects against chemical-induced hepatocellular carcinoma progression by modulating inflammation and cell proliferation in the liver | Authors: | Cabrera Galván, Juan José Araujo Ruano, Eduardo De Mirecki Garrido, Mercedes Pérez Rodríguez, David Guerra Hernández, Carlos Borja Aranda Tavío, Haidée Magdalena Guerra Rodríguez, Miguel Alfonso Brito Casillas, Yeray Melián Limiñana, Carlos Martínez Martín, María Soledad Fernández Pérez, Leandro Fco Recio Cruz, Carlota Pilar |
UNESCO Clasification: | 32 Ciencias médicas 3209 Farmacología |
Keywords: | Hepatocellular carcinoma SOCS2 STAT Inflammation Therapeutic target, et al |
Issue Date: | 2022 | Journal: | Biomedicine and Pharmacotherapy | Abstract: | Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide, but the precise intracellular mechanisms underlying the progression of this inflammation associated cancer are not well established. SOCS2 protein plays an important role in the carcinogenesis of different tumors by regulating cytokine signalling through the JAK/STAT axis. However, its role in HCC is unclear. Here, we investigate the role of SOCS2 in HCC progression and its potential as HCC biomarker. The effects of SOCS2 in HCC progression were evaluated in an experimental model of diethylnitrosamine (DEN)-induced HCC in C57BL/6 and SOCS2 deficient mice, in cultured hepatic cells, and in liver samples from HCC patients. Mice lacking SOCS2 showed higher liver tumor burden with increased malignancy grade, inflammation, fibrosis, and proliferation than their controls. Protein and gene expression analysis reported higher pSTAT5 and pSTAT3 activation, upregulation of different proteins involved in survival and proliferation, and increased levels of proinflammatory and pro-tumoral mediators in the absence of SOCS2. Clinically relevant, downregulated expression of SOCS2 was found in neoplasia from HCC patients compared to healthy liver tissue, correlating with the malignancy grade. In summary, our data show that lack of SOCS2 increases susceptibility to chemical-induced HCC and suggest the tumor suppressor role of this protein by regulating the oncogenic and inflammatory responses mediated by STAT5 and STAT3 in the liver. Hence, SOCS2 emerges as an attractive target molecule and potential biomarker to deepen in the study of HCC treatment. | URI: | http://hdl.handle.net/10553/119577 | ISSN: | 0753-3322 | DOI: | 10.1016/j.biopha.2022.114060 | Source: | Biomedicine & Pharmacotherapy [ISSN 0753-3322], v. 157, 114060, (Enero 2023) |
Appears in Collections: | Artículos |
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