{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T15:34:37Z","timestamp":1793892877619,"version":"4.8.0"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,17]],"date-time":"2025-05-17T00:00:00Z","timestamp":1747440000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,17]],"date-time":"2025-05-17T00:00:00Z","timestamp":1747440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Papillary thyroid cancer (PTC), the predominant thyroid cancer, exhibits different adverse outcomes. However, the underlying molecular mechanisms of PTC remain inadequately elucidated. An integrative analysis of multiple mRNA-seq datasets from Gene Expression Omnibus and The Cancer Genome Atlas reveals a crucial gene, prolyl 4-hydroxylase subunit alpha-2 (P4HA2), implicated in PTC progression. This study explored the expression pattern, functional role, and underlying molecular mechanism of P4HA2 in PTC. P4HA2 expression is significantly upregulated in PTC and correlates with aggressive clinicopathological features and a poor prognosis. P4HA2 knockdown effectively suppresses PTC cell proliferation, migration, and invasion, and induces apoptosis. Conversely, P4HA2 overexpression exerts opposing effects on these cancer cell phenotypes. In vivo assessments confirmed the tumor-promoting effects of P4HA2, including subcutaneous tumor formation and multiple-organ (lung and liver) metastasis. Multi-omics analyses identified glycolytic pathway activation as a hallmark of P4HA2-driven tumorigenesis, which was further validated by measuring the extracellular acidification rate and \u03b1-ketoglutarate level. Subsequent investigation revealed that tripartite motif-containing protein 21 (TRIM21) interacts with P4HA2 through the RING domain, promoting K48-linked and K63-linked ubiquitination followed by proteasome-dependent degradation of P4HA2. The knockdown of TRIM21 significantly enhances the proliferation, migration, and invasion of PTC cells, while also inducing apoptosis. Moreover, P4H inhibitors also displayed notable anti-tumor effects in PTC cells. These findings collectively elucidate a novel mechanism through which P4HA2 potentially contributes to PTC progression, providing a promising therapeutic target.<\/jats:p>","DOI":"10.1038\/s41419-025-07702-0","type":"journal-article","created":{"date-parts":[[2025,5,17]],"date-time":"2025-05-17T02:36:54Z","timestamp":1747449414000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Prolyl 4-hydroxylase subunit alpha-2 acts as a TRIM21 ubiquitination substrate to promote papillary thyroid cancer progression via the glycolytic pathway"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0399-6929","authenticated-orcid":false,"given":"Fengping","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7805-2052","authenticated-orcid":false,"given":"Qian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinkang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongkun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5891-0400","authenticated-orcid":false,"given":"Kun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YaZheng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuliang","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0475-5649","authenticated-orcid":false,"given":"Yuhong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8100-8511","authenticated-orcid":false,"given":"Wenling","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,17]]},"reference":[{"key":"7702_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209\u201349.","journal-title":"CA Cancer J Clin"},{"key":"7702_CR2","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","volume":"68","author":"F Bray","year":"2018","unstructured":"Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394\u2013424.","journal-title":"CA Cancer J Clin"},{"key":"7702_CR3","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1016\/S2213-8587(20)30115-7","volume":"8","author":"M Li","year":"2020","unstructured":"Li M, Dal Maso L, Vaccarella S. Global trends in thyroid cancer incidence and the impact of overdiagnosis. Lancet Diab Endocrinol. 2020;8:468\u201370.","journal-title":"Lancet Diab Endocrinol"},{"key":"7702_CR4","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21590","volume":"70","author":"RL Siegel","year":"2020","unstructured":"Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin. 2020;70:7\u201330.","journal-title":"CA Cancer J Clin"},{"key":"7702_CR5","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1089\/thy.2018.0128","volume":"29","author":"W Dong","year":"2019","unstructured":"Dong W, Horiuchi K, Tokumitsu H, Sakamoto A, Noguchi E, Ueda Y, et al. Time-varying pattern of mortality and recurrence from papillary thyroid cancer: lessons from a long-term follow-up. Thyroid. 2019;29:802\u20138.","journal-title":"Thyroid"},{"key":"7702_CR6","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1177\/000313480507100907","volume":"71","author":"YD Podnos","year":"2005","unstructured":"Podnos YD, Smith D, Wagman LD, Ellenhorn JDI. The implication of lymph node metastasis on survival in patients with well-differentiated thyroid cancer. Am Surg. 2005;71:731\u20134.","journal-title":"Am Surg"},{"key":"7702_CR7","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1038\/bjc.2012.380","volume":"107","author":"E Hatzimichael","year":"2012","unstructured":"Hatzimichael E, Lo Nigro C, Lattanzio L, Syed N, Shah R, Dasoula A, et al. The collagen prolyl hydroxylases are novel transcriptionally silenced genes in lymphoma. Br J Cancer. 2012;107:1423\u201332.","journal-title":"Br J Cancer"},{"key":"7702_CR8","doi-asserted-by":"publisher","first-page":"1406853","DOI":"10.1155\/2021\/1406853","volume":"2021","author":"J Lin","year":"2021","unstructured":"Lin J, Jiang L, Wang X, Wei W, Song C, Cui Y, et al. P4HA2 promotes epithelial-to-mesenchymal transition and glioma malignancy through the collagen-dependent PI3K\/AKT pathway. J Oncol. 2021;2021:1406853.","journal-title":"J Oncol"},{"key":"7702_CR9","doi-asserted-by":"publisher","first-page":"e9808","DOI":"10.1371\/journal.pone.0009808","volume":"5","author":"IJ Huijbers","year":"2010","unstructured":"Huijbers IJ, Iravani M, Popov S, Robertson D, Al-Sarraj S, Jones C, et al. A role for fibrillar collagen deposition and the collagen internalization receptor endo180 in glioma invasion. PLoS One. 2010;5:e9808.","journal-title":"PLoS One"},{"key":"7702_CR10","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202201247R","volume":"37","author":"X Li","year":"2023","unstructured":"Li X, Li Y, Liu B, Chen L, Lyu F, Zhang P, et al. P4HA2-mediated HIF-1\u03b1 stabilization promotes erdafitinib-resistance in FGFR3-alteration bladder cancer. FASEB J. 2023;37:e22840.","journal-title":"FASEB J"},{"key":"7702_CR11","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-1","volume":"14","author":"G Xiong","year":"2014","unstructured":"Xiong G, Deng L, Zhu J, Rychahou PG, Xu R. Prolyl-4-hydroxylase \u03b1 subunit 2 promotes breast cancer progression and metastasis by regulating collagen deposition. BMC Cancer. 2014;14:1.","journal-title":"BMC Cancer"},{"key":"7702_CR12","doi-asserted-by":"crossref","unstructured":"Lu X-H, Sang D, Zhang Y-R, Yuan Q. High expression of prolyl 4-hydroxylase subunit alpha-2 in lung adenocarcinoma indicates poor prognosis. Clinics (Sao Paulo. 2022;77:100123.","DOI":"10.1016\/j.clinsp.2022.100123"},{"key":"7702_CR13","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/s12906-023-04008-6","volume":"23","author":"F-F Tang","year":"2023","unstructured":"Tang F-F, Liu L, Tian X-T, Li N, Peng Y-X, Qian C-M, et al. Network pharmacological analysis of corosolic acid reveals P4HA2 inhibits hepatocellular carcinoma progression. BMC Complement Med Ther. 2023;23:171.","journal-title":"BMC Complement Med Ther"},{"key":"7702_CR14","doi-asserted-by":"publisher","first-page":"6049","DOI":"10.1038\/s41388-021-02000-3","volume":"40","author":"M Zhu","year":"2021","unstructured":"Zhu M, Peng R, Liang X, Lan Z, Tang M, Hou P, et al. P4HA2-induced prolyl hydroxylation suppresses YAP1-mediated prostate cancer cell migration, invasion, and metastasis. Oncogene. 2021;40:6049\u201356.","journal-title":"Oncogene"},{"key":"7702_CR15","doi-asserted-by":"publisher","first-page":"677831","DOI":"10.3389\/fcell.2021.677831","volume":"9","author":"C Shang","year":"2021","unstructured":"Shang C, Huang J, Guo H. Identification of an metabolic related risk signature predicts prognosis in cervical cancer and correlates with immune infiltration. Front Cell Dev Biol. 2021;9:677831.","journal-title":"Front Cell Dev Biol"},{"key":"7702_CR16","doi-asserted-by":"publisher","first-page":"601","DOI":"10.3892\/ol.2021.12862","volume":"22","author":"Y Wu","year":"2021","unstructured":"Wu Y, Zhang X, Wang J, Ji R, Zhang L, Qin J, et al. P4HA2 promotes cell proliferation and migration in glioblastoma. Oncol Lett. 2021;22:601.","journal-title":"Oncol Lett"},{"key":"7702_CR17","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","volume":"144","author":"D Hanahan","year":"2011","unstructured":"Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646\u201374.","journal-title":"Cell"},{"key":"7702_CR18","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/j.cell.2008.08.021","volume":"134","author":"PP Hsu","year":"2008","unstructured":"Hsu PP, Sabatini DM. Cancer cell metabolism: Warburg and beyond. Cell. 2008;134:703\u20137.","journal-title":"Cell"},{"key":"7702_CR19","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s13046-022-02254-z","volume":"41","author":"J Huang","year":"2022","unstructured":"Huang J, Sun W, Wang Z, Lv C, Zhang T, Zhang D, et al. FTO suppresses glycolysis and growth of papillary thyroid cancer via decreasing stability of APOE mRNA in an N6-methyladenosine-dependent manner. J Exp Clin Cancer Res. 2022;41:42.","journal-title":"J Exp Clin Cancer Res"},{"key":"7702_CR20","doi-asserted-by":"publisher","first-page":"4831","DOI":"10.3390\/molecules25204831","volume":"25","author":"J Li","year":"2020","unstructured":"Li J, Eu JQ, Kong LR, Wang L, Lim YC, Goh BC, et al. Targeting metabolism in cancer cells and the tumour microenvironment for cancer therapy. Molecules. 2020;25:4831.","journal-title":"Molecules"},{"key":"7702_CR21","doi-asserted-by":"publisher","first-page":"4372","DOI":"10.7150\/ijbs.72397","volume":"18","author":"X Zhu","year":"2022","unstructured":"Zhu X, Xue C, Kang X, Jia X, Wang L, Younis MH, et al. DNMT3B-mediated FAM111B methylation promotes papillary thyroid tumor glycolysis, growth and metastasis. Int J Biol Sci. 2022;18:4372\u201387.","journal-title":"Int J Biol Sci"},{"key":"7702_CR22","doi-asserted-by":"publisher","first-page":"2318","DOI":"10.1111\/cas.15772","volume":"114","author":"X Ji","year":"2023","unstructured":"Ji X, Lv C, Huang J, Dong W, Sun W, Zhang H. ALKBH5-induced circular RNA NRIP1 promotes glycolysis in thyroid cancer cells by targeting PKM2. Cancer Sci. 2023;114:2318\u201334.","journal-title":"Cancer Sci"},{"key":"7702_CR23","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.jaut.2012.01.014","volume":"39","author":"V Oke","year":"2012","unstructured":"Oke V, Wahren-Herlenius M. The immunobiology of Ro52 (TRIM21) in autoimmunity: a critical review. J Autoimmun. 2012;39:77\u201382.","journal-title":"J Autoimmun"},{"key":"7702_CR24","doi-asserted-by":"publisher","first-page":"1804","DOI":"10.1158\/0008-5472.CAN-15-2351","volume":"76","author":"LA Jolly","year":"2016","unstructured":"Jolly LA, Novitskiy S, Owens P, Massoll N, Cheng N, Fang W, et al. Fibroblast-mediated collagen remodeling within the tumor microenvironment facilitates progression of thyroid cancers driven by BrafV600E and Pten loss. Cancer Res. 2016;76:1804\u201313.","journal-title":"Cancer Res"},{"key":"7702_CR25","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1007\/s12020-022-03175-9","volume":"78","author":"J Niu","year":"2022","unstructured":"Niu J, Guo W, Chen Y-Z, Jiang N. Identification of the collagen family as prognostic biomarkers in papillary thyroid carcinoma. Endocrine. 2022;78:491\u2013506.","journal-title":"Endocrine"},{"key":"7702_CR26","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1093\/abbs\/gmab065","volume":"53","author":"R Shi","year":"2021","unstructured":"Shi R, Gao S, Zhang J, Xu J, Graham LM, Yang X, et al. Collagen prolyl 4-hydroxylases modify tumor progression. Acta Biochim Biophys Sin (Shanghai). 2021;53:805\u201314.","journal-title":"Acta Biochim Biophys Sin (Shanghai)"},{"key":"7702_CR27","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.ebiom.2019.06.048","volume":"45","author":"T Wang","year":"2019","unstructured":"Wang T, Fu X, Jin T, Zhang L, Liu B, Wu Y, et al. Aspirin targets P4HA2 through inhibiting NF-\u03baB and LMCD1-AS1\/let-7g to inhibit tumour growth and collagen deposition in hepatocellular carcinoma. EBioMedicine. 2019;45:168\u201380.","journal-title":"EBioMedicine"},{"key":"7702_CR28","doi-asserted-by":"publisher","first-page":"133","DOI":"10.3389\/fendo.2012.00133","volume":"3","author":"Saiselet","year":"2012","unstructured":"Saiselet, Floor M, Tarabichi S, Dom M, H\u00e9brant G, van Staveren WCG A, et al. Thyroid cancer cell lines: an overview. Front Endocrinol (Lausanne). 2012;3:133.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"7702_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s11658-022-00409-6","volume":"28","author":"L Zhang","year":"2023","unstructured":"Zhang L, Xu M, Zhang W, Zhu C, Cui Z, Fu H, et al. Three-dimensional genome landscape comprehensively reveals patterns of spatial gene regulation in papillary and anaplastic thyroid cancers: a study using representative cell lines for each cancer type. Cell Mol Biol Lett. 2023;28:1.","journal-title":"Cell Mol Biol Lett"},{"key":"7702_CR30","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/s41401-021-00658-9","volume":"43","author":"L Xu","year":"2022","unstructured":"Xu L, Yang T-Y, Zhou Y-W, Wu M-F, Shen J, Cheng J-L, et al. Bmal1 inhibits phenotypic transformation of hepatic stellate cells in liver fibrosis via IDH1\/\u03b1-KG-mediated glycolysis. Acta Pharm Sin. 2022;43:316\u201329.","journal-title":"Acta Pharm Sin"},{"key":"7702_CR31","doi-asserted-by":"publisher","first-page":"E1465","DOI":"10.1073\/pnas.1711257115","volume":"115","author":"S Xiang","year":"2018","unstructured":"Xiang S, Gu H, Jin L, Thorne RF, Zhang XD, Wu M. LncRNA IDH1-AS1 links the functions of c-Myc and HIF1\u03b1 via IDH1 to regulate the Warburg effect. Proc Natl Acad Sci USA. 2018;115:E1465\u2013E1474.","journal-title":"Proc Natl Acad Sci USA"},{"key":"7702_CR32","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201948183","volume":"21","author":"B Wang","year":"2020","unstructured":"Wang B, Ye Y, Yang X, Liu B, Wang Z, Chen S, et al. SIRT2-dependent IDH1 deacetylation inhibits colorectal cancer and liver metastases. EMBO Rep. 2020;21:e48183.","journal-title":"EMBO Rep."},{"key":"7702_CR33","doi-asserted-by":"publisher","first-page":"e00321","DOI":"10.1128\/JVI.00321-18","volume":"92","author":"B Xue","year":"2018","unstructured":"Xue B, Li H, Guo M, Wang J, Xu Y, Zou X, et al. TRIM21 promotes innate immune response to RNA viral infection through Lys27-linked polyubiquitination of MAVS. J Virol. 2018;92:e00321\u201318.","journal-title":"J Virol"},{"key":"7702_CR34","doi-asserted-by":"publisher","first-page":"968755","DOI":"10.3389\/fimmu.2022.968755","volume":"13","author":"X Chen","year":"2022","unstructured":"Chen X, Cao M, Wang P, Chu S, Li M, Hou P, et al. The emerging roles of TRIM21 in coordinating cancer metabolism, immunity and cancer treatment. Front Immunol. 2022;13:968755.","journal-title":"Front Immunol"},{"key":"7702_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05938-2","volume":"14","author":"K Xiao","year":"2023","unstructured":"Xiao K, Peng S, Lu J, Zhou T, Hong X, Chen S, et al. UBE2S interacting with TRIM21 mediates the K11-linked ubiquitination of LPP to promote the lymphatic metastasis of bladder cancer. Cell Death Dis. 2023;14:408.","journal-title":"Cell Death Dis"},{"key":"7702_CR36","doi-asserted-by":"publisher","first-page":"4919","DOI":"10.7150\/thno.85662","volume":"13","author":"Y Li","year":"2023","unstructured":"Li Y, Bao L, Zheng H, Geng M, Chen T, Dai X, et al. E3 ubiquitin ligase TRIM21 targets TIF1\u03b3 to regulate \u03b2-catenin signaling in glioblastoma. Theranostics. 2023;13:4919\u201335.","journal-title":"Theranostics"},{"key":"7702_CR37","doi-asserted-by":"publisher","first-page":"216158","DOI":"10.1016\/j.canlet.2023.216158","volume":"562","author":"X Sun","year":"2023","unstructured":"Sun X, Zhang K, Peng X, Zhou P, Qu C, Yang L, et al. HDAC4 mediated LHPP deacetylation enhances its destabilization and promotes the proliferation and metastasis of nasopharyngeal carcinoma. Cancer Lett. 2023;562:216158.","journal-title":"Cancer Lett"},{"key":"7702_CR38","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06893-9","volume":"9","author":"G Xiong","year":"2018","unstructured":"Xiong G, Stewart RL, Chen J, Gao T, Scott TL, Samayoa LM, et al. Collagen prolyl 4-hydroxylase 1 is essential for HIF-1\u03b1 stabilization and TNBC chemoresistance. Nat Commun. 2018;9:4456.","journal-title":"Nat Commun"},{"key":"7702_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2680-0","volume":"11","author":"S Hu","year":"2020","unstructured":"Hu S, Zhang C, Ni L, Huang C, Chen D, Shi K, et al. Stabilization of HIF-1\u03b1 alleviates osteoarthritis via enhancing mitophagy. Cell Death Dis. 2020;11:481.","journal-title":"Cell Death Dis"},{"key":"7702_CR40","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1016\/j.jid.2018.10.038","volume":"139","author":"A Atkinson","year":"2019","unstructured":"Atkinson A, Renziehausen A, Wang H, Lo Nigro C, Lattanzio L, Merlano M, et al. Collagen prolyl hydroxylases are bifunctional growth regulators in melanoma. J Invest Dermatol. 2019;139:1118\u201326.","journal-title":"J Invest Dermatol"},{"key":"7702_CR41","doi-asserted-by":"publisher","first-page":"2788","DOI":"10.7150\/jca.38401","volume":"11","author":"Y Cao","year":"2020","unstructured":"Cao Y, Han Q, Li J, Jia Y, Zhang R, Shi H. P4HA2 contributes to cervical cancer progression via inducing epithelial-mesenchymal transition. J Cancer. 2020;11:2788\u201399.","journal-title":"J Cancer"},{"key":"7702_CR42","doi-asserted-by":"publisher","first-page":"5182","DOI":"10.1038\/s41388-021-01919-x","volume":"40","author":"S Kaluz","year":"2021","unstructured":"Kaluz S, Zhang Q, Kuranaga Y, Yang H, Osuka S, Bhattacharya D, et al. Targeting HIF-activated collagen prolyl 4-hydroxylase expression disrupts collagen deposition and blocks primary and metastatic uveal melanoma growth. Oncogene. 2021;40:5182\u201391.","journal-title":"Oncogene"},{"key":"7702_CR43","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06137-9","volume":"14","author":"Y Lu","year":"2023","unstructured":"Lu Y, Zou R, Gu Q, Wang X, Zhang J, Ma R, et al. CRNDE mediated hnRNPA2B1 stability facilitates nuclear export and translation of KRAS in colorectal cancer. Cell Death Dis. 2023;14:611.","journal-title":"Cell Death Dis"},{"key":"7702_CR44","doi-asserted-by":"publisher","first-page":"216923","DOI":"10.1016\/j.canlet.2024.216923","volume":"592","author":"Z Wu","year":"2024","unstructured":"Wu Z, Zhang J, Jia Z, Yang Z, Liu S, Wang H, et al. TRIM21-mediated ubiquitylation of TAT suppresses liver metastasis in gallbladder cancer. Cancer Lett. 2024;592:216923.","journal-title":"Cancer Lett"},{"key":"7702_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2350-2","volume":"11","author":"W Si","year":"2020","unstructured":"Si W, Zhou J, Zhao Y, Zheng J, Cui L. SET7\/9 promotes multiple malignant processes in breast cancer development via RUNX2 activation and is negatively regulated by TRIM21. Cell Death Dis. 2020;11:151.","journal-title":"Cell Death Dis"},{"key":"7702_CR46","doi-asserted-by":"publisher","first-page":"5752","DOI":"10.1182\/bloodadvances.2022008241","volume":"7","author":"J Chen","year":"2023","unstructured":"Chen J, Cao W, Huang X, Chen Q, Ye S, Qu J, et al. TRIM21 enhances bortezomib sensitivity in multiple myeloma by halting prosurvival autophagy. Blood Adv. 2023;7:5752\u201370.","journal-title":"Blood Adv"},{"key":"7702_CR47","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/s42255-020-0172-2","volume":"2","author":"RJ DeBerardinis","year":"2020","unstructured":"DeBerardinis RJ, Chandel NS. We need to talk about the Warburg effect. Nat Metab. 2020;2:127\u20139.","journal-title":"Nat Metab"},{"key":"7702_CR48","doi-asserted-by":"crossref","unstructured":"Li T, Xu D, Ruan Z, Zhou J, Sun W, Rao B, et al. Metabolism\/immunity dual-regulation thermogels potentiating immunotherapy of glioblastoma through lactate-excretion inhibition and PD-1\/PD-L1 blockade. Adv Sci (Weinh). 2024;11:2310163.","DOI":"10.1002\/advs.202310163"},{"key":"7702_CR49","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2318904121","volume":"121","author":"L-J Chen","year":"2024","unstructured":"Chen L-J, Li JY-S, Nguyen P, He M, Chen ZB, Subramaniam S, et al. Single-cell RNA sequencing unveils unique transcriptomic signatures of endothelial cells and role of ENO1 in response to disturbed flow. Proc Natl Acad Sci USA. 2024;121:e2318904121.","journal-title":"Proc Natl Acad Sci USA"},{"key":"7702_CR50","doi-asserted-by":"crossref","unstructured":"Shixue Y, Qi Z, Dongyuan S, Xiaoteng C, Jixing Z, Qixue W, et al. HIF1\u03b1\/ATF3 partake PGK1 K191\/K192 succinylation by modulating P4HA1\/succinate signaling in glioblastoma. Neuro Oncol. 2024;26:1405\u201320.","DOI":"10.1093\/neuonc\/noae040"},{"key":"7702_CR51","doi-asserted-by":"publisher","first-page":"139150","DOI":"10.1016\/j.ijbiomac.2024.139150","volume":"291","author":"Y Ding","year":"2024","unstructured":"Ding Y, Liu M, Wang W, Li X. YTHDF3-induced degradation of P4HA2 mRNA inhibits glycolysis in papillary thyroid cancer through Hippo signaling pathway. Int J Biol Macromol. 2024;291:139150.","journal-title":"Int J Biol Macromol"},{"key":"7702_CR52","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1080\/15548627.2023.2249762","volume":"20","author":"W Li","year":"2024","unstructured":"Li W, Zhou C, Yu L, Hou Z, Liu H, Kong L, et al. Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer. Autophagy. 2024;20:114\u201330.","journal-title":"Autophagy"},{"key":"7702_CR53","doi-asserted-by":"publisher","first-page":"2061","DOI":"10.7150\/jca.66080","volume":"13","author":"L Sun","year":"2022","unstructured":"Sun L, Wu C, Ming J, Guo E, Zhang W, Li L, et al. EGLN1 induces tumorigenesis and radioresistance in nasopharyngeal carcinoma by promoting ubiquitination of p53 in a hydroxylase-dependent manner. J Cancer. 2022;13:2061\u201373.","journal-title":"J Cancer"},{"key":"7702_CR54","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.3724\/abbs.2023103","volume":"55","author":"Y Li","year":"2023","unstructured":"Li Y, Yuan T, Zhang H, Liu S, Lun J, Guo J, et al. PHD3 inhibits colon cancer cell metastasis through the occludin-p38 pathway. Acta Biochim Biophys Sin (Shanghai). 2023;55:1749\u201357.","journal-title":"Acta Biochim Biophys Sin (Shanghai)"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41419-025-07702-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-025-07702-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-025-07702-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,17]],"date-time":"2025-05-17T04:04:01Z","timestamp":1747454641000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41419-025-07702-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,17]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["7702"],"URL":"https:\/\/doi.org\/10.1038\/s41419-025-07702-0","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,17]]},"assertion":[{"value":"16 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 May 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Not applicable because this study was based exclusively on published literature.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"395"}}