Role of SOCS2 in Chemokine Signalling and its Impact on Hepatocellular Carcinoma Cells

Background and Aims: Hepatocellular carcinoma (HCC) is a primary liver cancer characterized by tumor development. In Pakistan, HCC is the eighth most common cancer and the seventh leading cause of liver cancer deaths. Research highlights that HCC is closely associated with chronic inflammation. The Suppressor of Cytokine Signaling (SOCS) genes, particularly SOCS2, play a crucial role in cellular responses to extracellular signals, primarily through the janus kinase (JAK), signal transducer and activator of transcription (STAT) pathways. SOCS2 modulates cytokine responses, thereby maintaining homeostasis. This study, therefore, aims to investigate the role of SOCS2 in chemokine signaling pathways, and its impact on HCC cell proliferation and migration.

Methods: Human liver cell line HepG2 was used in the current study. HepG2 cells were transfected with pEGFP-C2-SOCS2 plasmid to overexpress SOCS2. The differential expression of cytokines (e.g., IL-6, IL-1β), and chemokines (e.g., CXCR4, CXCL6, CXCL12, CXCL14, CCL20), as well as JAK2 and STAT3, was determined through qPCR. HEK293 cells were used as control cells. Assays were performed to analyze the impact of SOCS2 overexpression in HCC cells.

Results: Findings of the study revealed that SOCS2 significantly suppressed the expression of STAT3, cytokines IL-6 and IL-1β, and chemokines CXCR4, CXCL6, CXCL12, and CCL20. Additionally, SOCS2 inhibited the migration and proliferation abilities of HCC cells compared to the control cells.

Conclusion: The study concludes that SOCS2 significantly reduces the expression of inflammatory mediators in HepG2 cells, thereby suppressing HCC progression.

Publication History

Article published online:
20 January 2025