{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T02:11:40Z","timestamp":1780107100368,"version":"3.54.0"},"reference-count":32,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["DNA and Cell Biology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:p>\n                    Retinoblastoma (RB) arising from the retina\u2019s primitive neural precursor cells is a highly aggressive pediatric ocular malignancy. Ubiquitin-conjugating enzyme E2C (UBE2C) is implicated in carcinogenesis, but its role and mechanism in RB remain unexplored. Here, we aimed to explore the effect of UBE2C and its regulatory mechanism in an N6-methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) modification method in RB. The expression of UBE2C and methyltransferase-like 3 (METTL3) was determined by quantitative reverse transcription\u2013polymerase chain reaction (qRT-PCR) and Western blotting. After using shRNA and overexpression vectors to modulate the expression of UBE2C and METTL3 in RB cells, cell viability, proliferation, apoptosis, and phosphoinositide 3-kinase-protein kinase B (PI3K-AKT) pathway activity were assessed via cell counting kit-8, 5-ethynyl-2\u2032-deoxyuridine, flow cytometry, and Western blotting assays, respectively. The correlation between METTL3 and UBE2C in RB cells was verified by qRT-PCR, Western blotting, methylated RNA immunoprecipitation, mRNA stability assays. The results showed that UBE2C with high expression in RB enhanced RB cell survival via elevating cell viability and proliferation, as well as suppressing apoptosis. UBE2C activated the PI3K-AKT pathway by promoting the PI3K and AKT proteins. METTL3 upregulated UBE2C expression and enhanced UBE2C mRNA stability via m\n                    <jats:sup>6<\/jats:sup>\n                    A modification. In addition, upregulating METTL3 partly restored the negative effects of UBE2C downregulation on RB cells. In conclusion, METTL3 drives UBE2C overexpression through m\n                    <jats:sup>6<\/jats:sup>\n                    A modification, thereby activating the PI3K-AKT pathway to foster RB progression. This study identifies the METTL3\/UBE2C\/PI3K-AKT axis as a novel therapeutic target for RB.\n                  <\/jats:p>","DOI":"10.1089\/dna.2025.0074","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T05:13:19Z","timestamp":1749013999000},"page":"436-444","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["UBE2C, Regulated by n6-methyladenosine Methyltransferase METTL3, Is an Oncogene in Retinoblastoma via PI3K-AKT Pathway"],"prefix":"10.1177","volume":"44","author":[{"given":"Lan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Maternity and Child Health Hospital of Hubei Province, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8700-9879","authenticated-orcid":false,"given":"Songhua","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Wuhan Children\u2019s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"e_1_3_7_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-022-01500-4"},{"key":"e_1_3_7_3_1","doi-asserted-by":"publisher","DOI":"10.2103\/7\/jgo-22-516"},{"key":"e_1_3_7_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11010037"},{"key":"e_1_3_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-023-2499-2"},{"key":"e_1_3_7_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.992233"},{"key":"e_1_3_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00828-5"},{"key":"e_1_3_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0216-7"},{"key":"e_1_3_7_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/10799893.2024.2423100"},{"key":"e_1_3_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00450-x"},{"key":"e_1_3_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.134011"},{"key":"e_1_3_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-02998-6"},{"key":"e_1_3_7_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-19-0561"},{"key":"e_1_3_7_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2022.2032206"},{"key":"e_1_3_7_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/cimb46060317"},{"key":"e_1_3_7_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-023-00529-w"},{"key":"e_1_3_7_17_1","doi-asserted-by":"publisher","DOI":"10.4103\/IJO.IJO_2414_23"},{"key":"e_1_3_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e32844"},{"key":"e_1_3_7_19_1","doi-asserted-by":"publisher","DOI":"10.2089\/2\/j.issn.2095-3941.2018.0365"},{"key":"e_1_3_7_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13163949"},{"key":"e_1_3_7_21_1","doi-asserted-by":"publisher","DOI":"10.4103\/IJO.IJO_3172_22"},{"key":"e_1_3_7_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57114"},{"key":"e_1_3_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pedhc.2020.06.006"},{"key":"e_1_3_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2022.109221"},{"key":"e_1_3_7_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-024-12212-x"},{"key":"e_1_3_7_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-319639"},{"key":"e_1_3_7_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-022-02452-x"},{"key":"e_1_3_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15134"},{"key":"e_1_3_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2025.217734"},{"key":"e_1_3_7_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-023-02646-8"},{"key":"e_1_3_7_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15736"},{"key":"e_1_3_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apjo.2024.100058"},{"key":"e_1_3_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04817-6"}],"container-title":["DNA 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