Abstract
BackgroundThe study examines the expression and function of hypoxia-inducible gene 2 (HIG2) in hepatocellular carcinoma (HCC) tissues and cells.MethodsForty patients with HCC were included in the study. Bioinformatic analysis was used to analyze the clinical relevance of HIG2 expression in HCC tissue samples. Immunohistochemistry was employed to determine the expression of target proteins in tumor tissues. Hepatic HepG2 and SMMC-7721 cells were transfected with HIG2-targeting siRNA with Lipofectamine 2000. qRT-PCR was carried out to determine gene expression levels, while Western blotting was used to determine protein expression. A CCK-8 assay was performed to detect proliferation of cells, while migration and invasion of cells were studied by Transwell assay. Flow cytometry was carried out to detect surface markers and effector molecules in Nature killercells, as well as the killing effect of NK cells.ResultsHIG2 expression was upregulated in HCC. Silencing of HIG2 suppressed HCC cell migration and invasion. The killing effect of NK cells on HCC cells was enhanced after HIG2 was silenced in HCC cells. Conditioned media from HIG2-silenced SMMC-7721 cells inhibited the phenotype and function of NK cells. HCC cells with silenced expression of HIG2 modulated the activity of NK cells via STAT3. HIG2 promoted the evasion of HCC cells from killing by NK cells through upregulation of IL-10 expression.ConclusionThe study demonstrates that HIG2 activates the STAT3 signaling pathway in NK cells by promoting IL-10 release by HCC cells, thereby inhibiting the killing activity of NK cells, and subsequently promoting the recurrence and metastasis of HCC.
Highlights
The study examines the expression and function of hypoxia-inducible gene 2 (HIG2) in hepatocellular carcinoma (HCC) tissues and cells
HIG2 expression is upregulated in HCC The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to perform a preliminary assessment of the association between the expression of HIG2 gene in HCC tissues and prognosis of HCC
The expression of HIG2 mRNA in HepG2 and SMMC-7721 cells was significantly higher than that in tumor-adjacent tissues (P < 0.05; Fig. 1i). These results suggest that HIG2 expression is upregulated in HCC
Summary
The study examines the expression and function of hypoxia-inducible gene 2 (HIG2) in hepatocellular carcinoma (HCC) tissues and cells. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, and its incidence is higher in men than in women [1, 2]. In China, the incidence of HCC ranks fourth among all malignant tumors, and its mortality rate ranks second [3]. The role of the HIG2 gene in the occurrence and development of tumors has garnered significant research interest. Studies have shown that HIG2 plays an important role in the development and progression of renal cell carcinoma, cell lymphoma, epithelial ovarian cancer, transparent cell adenocarcinoma, and uterine cancer [11, 12]
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