{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:46:19Z","timestamp":1792043179534,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U2102203"],"award-info":[{"award-number":["U2102203"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82430084"],"award-info":[{"award-number":["82430084"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81672606"],"award-info":[{"award-number":["81672606"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2022MH206"],"award-info":[{"award-number":["ZR2022MH206"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Replication factor C subunit 4 (RFC4) dysregulation has been implicated in tumor progression and poor prognosis across multiple cancer types. Triple\u2010negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and poor outcomes, underscoring the need for effective therapeutic targets. However, the role of RFC4 in TNBC progression and metastasis remains unclear. In the present study, integrated bioinformatics analyses, together with validation in 80 clinical TNBC samples, showed that RFC4 was markedly upregulated in TNBC. In vitro functional assays and experiments in nude mouse models further demonstrated that elevated RFC4 expression contributed to TNBC progression (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05). Mechanistically, the upstream transcription factor TRIM28 (Tripartite motif\u2010containing 28) bound to the BS2 and BS3 sites within the\n                    <jats:italic>RFC4<\/jats:italic>\n                    promoter region, thereby activating\n                    <jats:italic>RFC4<\/jats:italic>\n                    transcription and increasing its expression. Furthermore, TRIM28 interacted with RFC4 and assembled K29\u2010linked ubiquitin chains at K205 and K217, enhancing RFC4 ubiquitination and protein stability in a manner dependent on TRIM28 ubiquitin ligase activity (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05). Finally, we showed that RFC4 activates the Ras\u2010associated protein 1 (Rap1)\u2010PI3K\u2013AKT pathway in a ubiquitination\u2010dependent manner, thereby enhancing TNBC cell proliferation and metastasis. Together, these findings suggest that the TRIM28\u2013RFC4 axis may represent a promising therapeutic target for TNBC.\n                  <\/jats:p>","DOI":"10.1002\/mco2.71043","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:55:23Z","timestamp":1791183323000},"source":"Crossref","is-referenced-by-count":0,"title":["TRIM28 Increases RFC4 Protein Expression to Promote Triple\u2010Negative Breast Cancer Progression"],"prefix":"10.1002","volume":"7","author":[{"given":"Cheng","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Pathology The Affiliated Hospital of Qingdao University  Qingdao Shandong China"},{"name":"Department of Pathology School of Basic Medicine Qingdao University  Qingdao Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery The First Affiliated Hospital of Chongqing Medical 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