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Building on our prior identification of ZWINT as a prognostic marker linked to metastasis, this study defines its critical functional role and regulatory mechanism. Multi-omics analysis revealed a strong association between ZWINT expression and metastatic processes across breast cancer subtypes. Functionally, ZWINT knockdown significantly inhibited breast cancer cell migration and invasion\u00a0in vitro\u00a0and dramatically reduced lung metastasis\u00a0in vivo. Mechanistically, we discovered that miR-495-3p directly targets and suppresses ZWINT expression, and this miR-495-3p\/ZWINT axis acts through inhibiting p38 MAPK pathway activation to suppress metastatic progression in vitro. Our findings demonstrate that ZWINT drives breast cancer metastasis and is negatively regulated by miR-495-3p. The newly identified miR-495-3p\/ZWINT\/p38 MAPK axis may provide a promising therapeutic target for suppressing breast cancer progression.<\/jats:p>","DOI":"10.1007\/s13577-025-01301-z","type":"journal-article","created":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T16:14:21Z","timestamp":1759594461000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["ZWINT down-regulated by miR-495-3p inhibited lung metastasis of breast cancer by blocking p38 MAPK signaling pathway activation"],"prefix":"10.1007","volume":"38","author":[{"given":"Ming-tao","family":"Shao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-wen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai-shuai","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-jie","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-mei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-wen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun-chen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,4]]},"reference":[{"key":"1301_CR1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. 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