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Contrary to its documented oncogenic role in a wide array of cancers, we herein demonstrate that DDX5 serves as a tumor suppressor in tongue cancer. The high expression of DDX5 is correlated with better prognosis for clinical tongue cancer patients. DDX5 downregulates the genes associated with tongue cancer progression. The knockdown of DDX5 promotes, while the overexpression of DDX5 inhibits, tongue cancer proliferation, development, and cisplatin resistance. Furthermore, the expression of DDX5 in tongue cancer is associated with immune cell infiltration in the tumor microenvironment. Specifically, the expression of DDX5 is associated with the reduced infiltration of M2 macrophages and increased infiltration of T cell clusters, which may contribute to anticancer effects in the tumor microenvironment. In this study, we establish DDX5 as a valuable prognostic biomarker and an important tumor suppressor in tongue cancer.<\/jats:p>","DOI":"10.3390\/cancers15245882","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T10:04:47Z","timestamp":1702893887000},"page":"5882","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["DDX5 Functions as a Tumor Suppressor in Tongue Cancer"],"prefix":"10.3390","volume":"15","author":[{"given":"Qingqing","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangqing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Long","sequence":"additional","affiliation":[{"name":"The Cancer Research Institute and the Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shangwei","family":"Zhong","sequence":"additional","affiliation":[{"name":"The Cancer Research Institute and the Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changhao","family":"Huang","sequence":"additional","affiliation":[{"name":"The Organ Transplant Center, Xiangya Hospital Central South University, Changsha 410000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7625-4766","authenticated-orcid":false,"given":"Jun-Li","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, China"},{"name":"The Cancer Research Institute and the Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China"},{"name":"National Health Commission Key Laboratory of Birth Defect Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41572-020-00224-3","article-title":"Head and neck squamous cell carcinoma","volume":"6","author":"Johnson","year":"2020","journal-title":"Nat. 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