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This study explored the role of HBx in mediating MICA\/B shedding. The expression of HBx, MICA\/B and HIF\u20101\u03b1 in HBV\u2010infected HCC was analysed using bioinformatics, and the localization of these proteins in tissues was verified using immunohistochemistry and immunofluorescence. HBx\u2010related signalling pathways were screened using RNA sequencing and KEGG pathway enrichment analyses. The expression of ADAM10 and MICA\/B was detected by Western blotting, and the dynamic changes of MICA\/B in the membrane and supernatant were evaluated by flow cytometry and ELISA. The HIF\u20101\u03b1 inhibitor (LW\u20106) and ADAM10 inhibitor (GI254023X) were used to treat the HCC cells. The killing effect of NK\u201092 cells on HCC cells was evaluated using lactate dehydrogenase release, cytotoxicity assays, clone formation and live\u2010cell imaging, and the secretion levels of IFN\u2010\u03b3, IL\u20102 and IL\u201010 were measured. These results indicated that HBx, MICA\/B and HIF\u20101\u03b1 were highly expressed in HBV\u2010infected HCC tissues. HBx promotes shedding of MICA\/B from HCC cell membranes by upregulating the activity of ADAM10. LW\u20106 reversed the induction effect of HBx on ADAM10 and GI254023X significantly restored MICA\/B levels on the membrane surface of HCC cells. Overexpression of HBx increases the resistance of HCC cells to NK\u201092 cells and inhibits the secretion of IFN\u2010\u03b3, IL\u20102 and IL\u201010. In conclusion, HBx regulates the expression of ADAM10 by activating the HIF\u20101\u03b1 signalling pathway. ADAM10 cuts MICA\/B shedding from the membrane surface of HCC cells, resulting in escape attack by NK\u201092 cells.<\/jats:p>","DOI":"10.1111\/jcmm.71081","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T11:32:27Z","timestamp":1772969547000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>HBx<\/scp>\n                    Promotes Liver Cancer Cells to Escape\n                    <scp>NK<\/scp>\n                    \u201092 Cell Attack by Mediating\n                    <scp>ADAM10<\/scp>\n                    to Enzyme Cut\n                    <scp>MICA<\/scp>\n                    \/B Shedding From Cancer Cell Membrane"],"prefix":"10.1111","volume":"30","author":[{"given":"Kailin","family":"Huang","sequence":"first","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine, Ministry of Education Hainan Medical University  Haikou Hainan P. R. 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