Suppressors of Cytokine Signaling and Hepatocellular Carcinoma

Abstract

Cytokines are secreted soluble glycoproteins that regulate cellular growth, proliferation, and differentiation. Suppressors of cytokine signaling (SOCS) proteins negatively regulate cytokine signaling and form a classical negative feedback loop in the signaling pathways. There are eight members of the SOCS family. The SOCS proteins are all comprised of a loosely conserved N-terminal domain, a central Src homology 2 (SH2) domain, and a highly conserved SOCS box at the C-terminus. The role of SOCS proteins has been implicated in the regulation of cytokines and growth factors in liver diseases. The SOCS1 and SOCS3 proteins are involved in immune response and inhibit protective interferon signaling in viral hepatitis. A decreased expression of SOCS3 is associated with advanced stage and poor prognosis of patients with hepatocellular carcinoma (HCC). DNA methylations of SOCS1 and SOCS3 are found in HCC. Precise regulation of liver regeneration is influenced by stimulatory and inhibitory factors after partial hepatectomy (PH), in particular, SOCS2 and SOCS3 are induced at an early time point after PH. Evidence supporting the important role of SOCS signaling during liver regeneration also supports a role of SOCS signaling in HCC. Immuno-oncology drugs are now the first-line therapy for advanced HCC. The SOCS can be potential targets for HCC in terms of cell proliferation, cell differentiation, and immune response. In this literature review, we summarize recent findings of the SOCS family proteins related to HCC and liver diseases.

Expression characteristics, immune signature, and prognostic value of the SOCS family identified by multiomics integrative analysis in liver cancer

“…More and more studies suggested that the SOCS family genes were the key factors in the occurrence, development, invasion and angiogenesis of malignant tumors [2,22] . However, only a limited number of studies have shown that SOCS family member are associated with HCC [23] , and the exact biological function of the SOCS family in HCC remains unclear.…”

Increased expression of miR-194-5p through the circPVRL3/miR-194-5p/SOCS2 axis promotes proliferation and metastasis in pancreatic ductal adenocarcinoma by activating the PI3K/AKT signaling pathway

“…SOCS2 is one of the SOCS family members. Previous studies indicated that a decreased expression of SOCS2 was associated with the progression and poor prognosis of hepatocellular carcinoma (HCC) [ 46 ]. Similarly, SOCS2 was identified as a target of miR-196a and miR-196b that modulated the JAK/STAT signaling pathway affecting the progression of HCC [ 47 ].…”

Inflammasome-Mediated Cytokines: A Key Connection between Obesity-Associated NASH and Liver Cancer Progression

“…Promising cytokine immunotherapies currently under investigation are pegylated INF [ 117 ], INF-β [ 118 ], IL-2 in adenoviral vector [ 119 ], IL-6 [ 120 ], IL-7 [ 121 ], TNF-α [ 122 ], and TGF-beta [ 123 ]. In addition, intracellular biosignaling pathways related to cytokines are also a promising approach [ 124 ].…”