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This work attempted to reveal the underlying mechanism of XPD in HCC. In this study, XPD and miR\u201029a\u20103p were down\u2010regulated, and MIAT and COL4A1 were up\u2010regulated in tumor tissues of HCC patients. The same phenomena were also observed in HCC cell lines. XPD overexpression enhanced E\u2010cadherin expression, reduced N\u2010cadherin and Vimentin expression, and repressed the migration and invasion of HepG2 and Hep3B cells. MIAT or COL4A1 overexpression reversed the effect of XPD on the invasion, migration, and epithelial\u2010mesenchymal transition (EMT) of HCC cells. MIAT overexpression\u2010mediated promotion of malignant phenotypes of HCC cells was reversed by COL4A1 deficiency. In terms of mechanics, MIAT enhanced COL4A1 expression by sponging miR\u201029a\u20103p. XPD interacted with P53. XPD overexpression repressed MIAT expression, which was abrogated by P53 silencing. Thus, XPD recruited P53 to repress MIAT expression. In\u00a0vivo, XPD up\u2010regulation inhibited tumor growth and reduced the metastatic lesions in intrahepatic, lung, and kidney tissues of mice. In conclusion, this study demonstrated that XPD recruited P53 to regulate the MIAT\/miR\u201029a\u20103p\/COL4A1 axis, which contributed to inhibiting migration, invasion, EMT, and metastasis of HCC. Thus, XPD may be a valuable target for HCC treatment.<\/jats:p>","DOI":"10.1096\/fj.202402908r","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T10:16:00Z","timestamp":1747304160000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>XPD<\/scp>\n                    Regulates\n                    <scp>MIAT<\/scp>\n                    \/\n                    <scp>miR<\/scp>\n                    \u201029a\u20103p\/\n                    <scp>COL4A1<\/scp>\n                    Axis to Impede Hepatocellular Carcinoma Development"],"prefix":"10.1096","volume":"39","author":[{"given":"Qi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Nanchang University  Nanchang Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qichao","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Affiliated Hospital of Jiujiang University  Jiujiang Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9349-9811","authenticated-orcid":false,"given":"Hao","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Nanchang University  Nanchang Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","unstructured":"J. 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