Abstract
OBJECTIVE: To investigate the effects of Siglec-5 on hepatocellular carcinoma and the mechanism of action. The interactions and expression changes between Siglec-5 and Siglec-14 not only affect immune cell function, but may also influence tumor progression. A deeper understanding of the mechanisms regulating their balance could provide new insights and strategies for hepatocellular carcinoma treatment. METHODS: A cell co-culture model was established. Western blotting was used to detect protein expression in different groups. The CCK-8 assay was employed to observe the proliferation of HepG2 hepatocellular carcinoma cells, and the Transwell assay was used to examine their migration. Tumorigenic capacity of HepG2 cells detected by subcutaneous transplantation tumor assay in nude mice. RESULTS: Overexpression of Siglec-5 under hypoxic conditions resulted in increased levels of SHP2 and arginase-1 proteins and decreased levels of P-SYK, IL-1β, and TNFα proteins. Addition of SHP2 inhibitor under hypoxic conditions or Siglec-5 overexpression resulted in increased expression of P-SYK and NOX4 proteins and decreased levels of arginase-1. When Siglec-5 expression was inhibited under hypoxic conditions, the levels of P-SHP2 and arginase-1 were decreased, whereas the levels of P-SYK, IL-1β, and TNFα were increased. The expression of P-SYK, NOX4, IL-1β, and TNFα was decreased, whereas the levels of arginase-1 were increased after the use of SYK inhibitors under hypoxic conditions that inhibited Siglec-5 expression. The proliferation, migration and tumorigenicity of HepG2 cells were increased when Siglec-5 was overexpressed under hypoxic conditions, while the proliferation, migration and tumorigenicity of HepG2 cells were decreased when Siglec-5 was inhibited under hypoxic conditions. CONCLUSION: Hypoxia suppressed the Siglec-5 signaling in TAMs via modulating the balance of SHP2/SYK activation in hepatocellular carcinoma.