{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T21:17:12Z","timestamp":1788988632611,"version":"build-2803163510"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality, and TMEM160 is potentially involved in tumor progression and immune escape. This study aimed to determine the expression pattern and clinical relevance of TMEM160 in HCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      TMEM160 expression was analyzed in public HCC cohorts and validated in 76 paired HCC tissues and adjacent non-tumor tissues. Survival associations were assessed using Kaplan\u2013Meier analysis. TMEM160 was silenced in Huh7 and Hep3B cells and overexpressed in SNU449 cells, followed by assays of proliferation, invasion, and endothelial tube formation using HUVECs conditioned medium. PD-L1 protein expression was detected by Western blotting. HCC cells were co-cultured with PBMCs, followed by ELISA detection of IFN-\u03b3, IL-2, IL-10, and TGF-\u03b2 secretion and flow cytometric analysis of CD8\n                      <jats:sup>+<\/jats:sup>\n                      IFN-\u03b3\n                      <jats:sup>+<\/jats:sup>\n                      T cells to evaluate immune-related effects. Mechanistically, PI3K and AKT phosphorylation changes were examined, and VEGFA rescue experiments were performed by overexpressing VEGFA in TMEM160-silenced HCC cells. Additionally, a subcutaneous murine tumor model was used to validate\n                      <jats:italic>in vivo<\/jats:italic>\n                      effects, and tumor tissues were examined by H&amp;amp;E staining, immunohistochemistry, and Western blotting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TMEM160 was increased in HCC tissues and HCC cells, and high TMEM160 expression was associated with poorer overall survival. TMEM160 knockdown reduced HCC cell viability, invasion, HUVEC tube formation with decreased VEGFA expression. TMEM160 knockdown also decreased PD-L1 protein levels in HCC cells. TMEM160 modulation was accompanied by concordant changes in PI3K\/AKT phosphorylation, and VEGFA overexpression increased PI3K\/AKT phosphorylation and partially rescued inhibitory phenotypes caused by TMEM160 silencing.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , TMEM160 knockdown suppressed tumor growth, reduced TMEM160-positive and VEGFA-positive proportions, increased interferon-\u03b3 (IFN-\u03b3) positivity, and decreased p-PI3K\/PI3K and p-AKT\/AKT ratios in tumor tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings supported that TMEM160 might affect VEGFA-associated PI3K\/AKT signaling to promote malignant phenotypes in HCC, suggesting TMEM160 as a candidate molecular target for further investigation.<\/jats:p>\n                  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