{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T02:28:54Z","timestamp":1789612134282,"version":"build-2803163510"},"reference-count":28,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871231"],"award-info":[{"award-number":["81871231"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Youth Innovation and Science and Technology Plan of Colleges and Universities in Shandong Province","award":["2019KJK016"],"award-info":[{"award-number":["2019KJK016"]}]},{"name":"Shandong Taishan Scholars Young Experts Program","award":["tsqn202103056"],"award-info":[{"award-number":["tsqn202103056"]}]},{"name":"The Natural Science Foundation of Shandong Province","award":["ZR2023MH082"],"award-info":[{"award-number":["ZR2023MH082"]}]},{"name":"Qingdao Natural Science Foundation Key Project","award":["24\u20138-4-zrjj-8-jch"],"award-info":[{"award-number":["24\u20138-4-zrjj-8-jch"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cervical cancer is a gynecological malignancy closely associated with high-risk human papillomavirus infection. Trim45, a member of the E3 ubiquitin ligase family, is highly expressed in cervical cancer tissues; however, its specific mechanistic contribution to disease progression remains incompletely understood. By integrating single-cell sequencing, functional assays, and molecular profiling, we found that single-cell sequencing and IHC analyses revealed high Trim45 expression in cervical cancer tissues from patients with HPV-18 infection. Furthermore, we uncovered a novel mechanism by which Trim45 promotes cervical cancer progression: Trim45 suppresses the cGAS\/STING signaling pathway activity by mediating ANXA2, which subsequently upregulates the expression of the key glycolytic enzymes HK2 and ENO2, enhances the aerobic glycolysis capacity of tumor cells, and ultimately promotes cervical cancer proliferation and metastasis. Collectively, these findings elucidate the molecular mechanism by which Trim45 drives the malignant progression of cervical cancer through the \"ANXA2-cGAS\/STING-glycolysis\" axis.<\/jats:p>\n                  <jats:p>Statement of Integration, Innovation and Insight This study integrates single-cell sequencing and functional assays to reveal that Trim45, highly expressed in HPV-18 positive cervical cancer, suppresses the cGAS\/STING innate immune signaling pathway by mediating ANXA2. This suppression subsequently upregulates the key glycolytic enzymes HK2 and ENO2, thereby enhancing aerobic glycolysis in tumor cells, and promotes proliferation and metastasis. These findings uncover a novel Trim45-ANXA2-cGAS\/STING-glycolysis axis, offering potential therapeutic co-targets.<\/jats:p>","DOI":"10.1093\/intbio\/zyag009","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T11:47:04Z","timestamp":1778845624000},"source":"Crossref","is-referenced-by-count":1,"title":["Trim45 promotes the occurrence and development of cervical cancer by inhibiting the cGAS\/STING signaling pathway"],"prefix":"10.1093","volume":"18","author":[{"given":"Huhu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Genetics and Cell Biology, School of Basic Medicine, Qingdao University , Qingdao, Ningxia road, Shandong 266071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Applied Biology, Shanxi Key Laboratory of Nucleic Acid Biopesticides, Shanxi University , Nan Zhonghuan Dong road, Taiyuan 030006, Shanxi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Banghui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Affiliated Hospital of Qingdao University , No. 59 Haier Road, Qingdao 266100, Shandong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingxi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Genetics and Cell Biology, School of Basic Medicine, Qingdao University , Qingdao, Ningxia road, Shandong 266071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Dong","sequence":"additional","affiliation":[{"name":"School of Physical Education, Fuyang Nomal University , Qinghe West Road, Fuyang 236041, Anhui ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Integrated Traditional Chinese and Western Medicine, Jining Medical University , Hehua road, Jining 272067, Shandong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5545-9674","authenticated-orcid":false,"given":"Bing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Genetics and Cell Biology, School of Basic Medicine, Qingdao University , Qingdao, Ningxia road, Shandong 266071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"2026060304414541000_ref1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/CMR.16.1.1-17.2003","article-title":"Human papillomavirus and cervical cancer","volume":"16","author":"Burd","year":"2003","journal-title":"Clin Microbiol Rev"},{"key":"2026060304414541000_ref2","doi-asserted-by":"publisher","first-page":"111192","DOI":"10.1016\/j.cellsig.2024.111192","article-title":"IRAK1 deficiency potentiates the efficacy of radiotherapy in repressing cervical cancer development","volume":"119","author":"Chen","year":"2024","journal-title":"Cell Signal"},{"key":"2026060304414541000_ref3","doi-asserted-by":"publisher","first-page":"2571","DOI":"10.1002\/cncr.35334","article-title":"Top advances of the year: cervical cancer","volume":"130","author":"Duska","year":"2024","journal-title":"Cancer"},{"key":"2026060304414541000_ref4","doi-asserted-by":"publisher","first-page":"111115","DOI":"10.1016\/j.cellsig.2024.111115","article-title":"LOC644656 promotes cisplatin resistance in cervical cancer by recruiting ZNF143 and activating the transcription of E6-AP","volume":"117","author":"Li","year":"2024","journal-title":"Cell Signal"},{"key":"2026060304414541000_ref5","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1001\/jamaoncol.2025.0146","article-title":"Adjuvant chemoradiotherapy vs radiotherapy alone for patients with intermediate-risk cervical cancer","volume":"11","author":"Agust\u00ed","year":"2025","journal-title":"JAMA Oncol"},{"key":"2026060304414541000_ref6","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1186\/s13046-023-02758-2","article-title":"FAT4 overexpression promotes antitumor immunity by regulating the \u03b2-catenin\/STT3\/PD-L1 axis in cervical cancer","volume":"42","author":"Wang","year":"2023","journal-title":"J Exp Clin Cancer Res"},{"key":"2026060304414541000_ref7","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.semcancer.2024.11.002","article-title":"Remodeling of tumor microenvironment by cellular senescence and immunosenescence in cervical cancer","volume":"108","author":"He","year":"2025","journal-title":"Semin Cancer Biol"},{"key":"2026060304414541000_ref8","doi-asserted-by":"publisher","first-page":"111919","DOI":"10.1016\/j.cellsig.2025.111919","article-title":"Trim45: an emerging E3 ubiquitin ligases in cancer","volume":"134","author":"Zhang","year":"2025","journal-title":"Cell Signal"},{"key":"2026060304414541000_ref9","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1186\/s12974-023-02959-8","article-title":"TRIM45 aggravates microglia pyroptosis via Atg5\/NLRP3 axis in septic encephalopathy","volume":"20","author":"Huang","year":"2023","journal-title":"J Neuroinflammation"},{"key":"2026060304414541000_ref10","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.bbrc.2012.05.090","article-title":"TRIM45 negatively regulates NF-\u03baB-mediated transcription and suppresses cell proliferation","volume":"423","author":"Shibata","year":"2012","journal-title":"Biochem Biophys Res Commun"},{"key":"2026060304414541000_ref11","doi-asserted-by":"publisher","first-page":"299","DOI":"10.2174\/1566524019666191017143833","article-title":"TRIM45 suppresses the development of non-small cell lung cancer","volume":"20","author":"Peng","year":"2020","journal-title":"Curr Mol Med"},{"key":"2026060304414541000_ref12","doi-asserted-by":"publisher","first-page":"2063","DOI":"10.1038\/s41388-024-03056-7","article-title":"TRIM45 facilitates NASH-progressed HCC by promoting fatty acid synthesis via catalyzing FABP5 ubiquitylation","volume":"43","author":"Li","year":"2024","journal-title":"Oncogene"},{"key":"2026060304414541000_ref13","doi-asserted-by":"publisher","first-page":"e2831","DOI":"10.1038\/cddis.2017.149","article-title":"TRIM45 functions as a tumor suppressor in the brain via its E3 ligase activity by stabilizing p53 through K63-linked ubiquitination","volume":"8","author":"Zhang","year":"2017","journal-title":"Cell Death Dis"},{"key":"2026060304414541000_ref14","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/s41418-023-01242-w","article-title":"Activating STING\/TBK1 suppresses tumor growth via degrading HPV16\/18 E7 oncoproteins in cervical cancer","volume":"31","author":"Huang","year":"2024","journal-title":"Cell Death Differ"},{"key":"2026060304414541000_ref15","doi-asserted-by":"publisher","first-page":"e1009028","DOI":"10.1371\/journal.ppat.1009028","article-title":"Vesicular trafficking permits evasion of cGAS\/STING surveillance during initial human papillomavirus infection","volume":"16","author":"Uhlorn","year":"2020","journal-title":"PLoS Pathog"},{"key":"2026060304414541000_ref16","doi-asserted-by":"publisher","first-page":"111914","DOI":"10.1016\/j.cellsig.2025.111914","article-title":"STING agonists: a range of eminent mediators in cancer immunotherapy","volume":"134","author":"Wen","year":"2025","journal-title":"Cell Signal"},{"key":"2026060304414541000_ref17","doi-asserted-by":"publisher","first-page":"e28220","DOI":"10.1002\/jmv.28220","article-title":"SARS-CoV-2, HIV, and HPV: convergent evolution of selective regulation of cGAS-STING signaling","volume":"95","author":"Shen","year":"2023","journal-title":"J Med Virol"},{"key":"2026060304414541000_ref18","doi-asserted-by":"publisher","first-page":"139040","DOI":"10.1016\/j.ijbiomac.2024.139040","article-title":"DHAV-1 3C protein promotes viral proliferation by antagonizing type I interferon via upregulating the ANXA2 protein","volume":"291","author":"Zhang","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"2026060304414541000_ref19","doi-asserted-by":"publisher","first-page":"1586806","DOI":"10.3389\/fimmu.2025.1586806","article-title":"The role of tumor-associated macrophages in HPV induced cervical cancer","volume":"16","author":"Chen","year":"2025","journal-title":"Front Immunol"},{"key":"2026060304414541000_ref20","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1172\/JCI129497","article-title":"HPV16 drives cancer immune escape via NLRX1-mediated degradation of STING","volume":"130","author":"Luo","year":"2020","journal-title":"J Clin Invest"},{"key":"2026060304414541000_ref21","doi-asserted-by":"publisher","first-page":"12669","DOI":"10.1093\/nar\/gkae810","article-title":"The TRIM-NHL RNA-binding protein brain tumor coordinately regulates expression of the glycolytic pathway and vacuolar ATPase complex","volume":"52","author":"Connacher","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"2026060304414541000_ref22","doi-asserted-by":"publisher","first-page":"119943","DOI":"10.1016\/j.jep.2025.119943","article-title":"Enhancement of endometrial receptivity by Bushen Zhuyun decoction via cryptotanshinone-mediated TRIM28 induction and HIF-1\u03b1 suppression","volume":"350","author":"Tang","year":"2025","journal-title":"J Ethnopharmacol"},{"key":"2026060304414541000_ref23","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/s41419-025-07923-3","article-title":"NLRP12 decreases TRIM25-mediated HK2 degradation to promote glycolysis and H3K18la in gastric cancer","volume":"16","author":"Zhou","year":"2025","journal-title":"Cell Death Dis"},{"key":"2026060304414541000_ref24","doi-asserted-by":"publisher","first-page":"199","DOI":"10.3724\/abbs.2024014","article-title":"UBA3 promotes the occurrence and metastasis of intrahepatic cholangiocarcinoma through MAPK signaling pathway","volume":"56","author":"Zhang","year":"2024","journal-title":"Acta Biochim Biophys Sin"},{"key":"2026060304414541000_ref25","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1186\/s12967-023-04613-6","article-title":"Bufalin targeting CAMKK2 inhibits the occurrence and development of intrahepatic cholangiocarcinoma through Wnt\/\u03b2-catenin signal pathway","volume":"21","author":"Zhang","year":"2023","journal-title":"J Transl Med"},{"key":"2026060304414541000_ref26","doi-asserted-by":"publisher","first-page":"109790","DOI":"10.1016\/j.biopha.2019.109790","article-title":"IFI16 promotes cervical cancer progression by upregulating PD-L1 in immunomicroenvironment through STING-TBK1-NF-kB pathway","volume":"123","author":"Cai","year":"2020","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"2026060304414541000_ref27","doi-asserted-by":"publisher","DOI":"10.1093\/intbio\/zyaf017","article-title":"The diagnosis and prognostic value and biological function of annexin A2 in hepatocellular carcinoma: a bioinformatic and experimental study","volume":"17","author":"Li","year":"2025","journal-title":"Integr Biol"},{"key":"2026060304414541000_ref28","doi-asserted-by":"publisher","first-page":"1141331","DOI":"10.3389\/fcell.2023.1141331","article-title":"Annexin a protein family: focusing on the occurrence, progression and treatment of cancer","volume":"11","author":"Zhang","year":"2023","journal-title":"Front Cell Dev Biol"}],"container-title":["Integrative Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ib\/article-pdf\/doi\/10.1093\/intbio\/zyag009\/68388466\/zyag009.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ib\/article-pdf\/doi\/10.1093\/intbio\/zyag009\/68388466\/zyag009.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:42:02Z","timestamp":1780476122000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ib\/article\/doi\/10.1093\/intbio\/zyag009\/8693239"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":28,"URL":"https:\/\/doi.org\/10.1093\/intbio\/zyag009","relation":{},"ISSN":["1757-9708"],"issn-type":[{"value":"1757-9708","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2026,1]]},"article-number":"zyag009"}}