{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:05:07Z","timestamp":1753877107350,"version":"3.41.2"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:00:00Z","timestamp":1729728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The role of MIR654 in Burkitt lymphoma (BL) and whether it impacts expression of MYC and its downstream activated MIR9 is not known. Expression of MYC, MYCN, MYCL, MIR9\/3P, MIR654\/5P, and MIR654\/3P was assessed by quantitative reverse-transcription polymerase chain reaction in biopsy samples from Epstein-Barr virus\u2013negative (EBV\u2212) and EBV+ BL patients and BL cell lines. Effects of modulation of MIR9\/3P and MIR654\/3P on cell proliferation, apoptosis, and chemosensitivity were evaluated. Luciferase reporter assay was performed to validate the putative target of MIR654\/5P. Effects of MIR9\/3P and MIR654\/3P on tumor burden and disease outcome were evaluated using xenograft model of BL. Expression of MYC, MYCN, and MIR9\/3P was higher in all BL patient samples and cell lines. Expression of MIR654\/3P was downregulated in EBV\u2212 BL patient samples and cell lines compared with either noncancer lymphoid-reactive hyperplasia or EBV+ samples and cell lines. Additionally, MIR654\/3P overexpression inhibited cell proliferation, induced apoptosis, and increased chemosensitivity in EBV\u2212 BL cell lines. Luciferase reporter assay confirmed that MYC is a target of MIR654\/3P in both EBV\u2212 and EBV+ BL cell lines; however, the effect of MIR654\/3P-mediated targeting of MYC is overridden in EBV+ cells. Administration of MIR654\/3P mimic or MIR9\/3P antagomir in the xenograft model decreased tumor burden and increased survival. Combined intervention with MIR654\/3P mimic and MIR9\/3P antagomir had synergistic action on decreasing tumor burden and improving disease outcome. MIR654\/3P, as a putative tumor suppressor in EBV\u2212 BL, collaborating with MIR9\/3P might serve as a therapeutic agent to treat EBV\u2212 BL patients in combination with existing chemotherapy and immunotherapy regimes.<\/jats:p>","DOI":"10.1093\/jleuko\/qiae237","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T16:19:27Z","timestamp":1729786767000},"source":"Crossref","is-referenced-by-count":0,"title":["Reversible role of <i>MIR654\/3P<\/i> and <i>MIR9\/3P<\/i> in pathogenesis of Epstein-Barr virus\u2013negative, but not Epstein-Barr virus\u2013positive, Burkitt lymphoma"],"prefix":"10.1093","volume":"117","author":[{"given":"Yu","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Hematology, Huainanchaoyang Hospital , No. 15 Renmin South Road, Tianjia 'an District, Huainan 232007, Anhui ,","place":["China"]},{"name":"Department of Hematology, First Affiliated Hospital of Anhui Medical University , 218 Jixi Road, Hefei 230022, Anhui ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3647-9983","authenticated-orcid":false,"given":"Wenhua","family":"Fu","sequence":"additional","affiliation":[{"name":"Cancer Center, Huainanchaoyang Hospital , No. 15 Renmin South Road, Tianjia 'an District, Huainan 232007, Anhui ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"issue":"19","key":"2025033004023924900_qiae237-B1","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1056\/NEJM199605093341906","article-title":"Non-Hodgkin's lymphoma in childhood","volume":"334","author":"Sandlund","year":"1996","journal-title":"N Engl J Med"},{"issue":"2","key":"2025033004023924900_qiae237-B2","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1002\/1097-0142(196103\/04)14:2&lt;258::AID-CNCR2820140206&gt;3.0.CO;2-7","article-title":"Malignant lymphoma in African children. I. A clinical syndrome","volume":"14","author":"Burkitt","year":"1961","journal-title":"Cancer"},{"issue":"6","key":"2025033004023924900_qiae237-B3","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1182\/blood-2010-04-278796","article-title":"Morbidity and mortality in long-term survivors of Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study","volume":"117","author":"Castellino","year":"2011","journal-title":"Blood"},{"issue":"6","key":"2025033004023924900_qiae237-B4","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1016\/j.hoc.2016.07.009","article-title":"Update on Burkitt lymphoma","volume":"30","author":"Dunleavy","year":"2016","journal-title":"Hematol Oncol Clin North Am"},{"key":"2025033004023924900_qiae237-B5","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/S0065-230X(08)60470-4","article-title":"The pathogenesis of Burkitt\u2019s lymphoma","volume":"55","author":"Magrath","year":"1990","journal-title":"Adv Cancer Res"},{"issue":"3","key":"2025033004023924900_qiae237-B6","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1002\/pbc.22047","article-title":"Sporadic childhood Burkitt lymphoma incidence in the United States during 1992-2005","volume":"53","author":"Mbulaiteye","year":"2009","journal-title":"Pediatr Blood Cancer"},{"issue":"9822","key":"2025033004023924900_qiae237-B7","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1016\/S0140-6736(11)61177-X","article-title":"Burkitt\u2019s lymphoma","volume":"379","author":"Molyneux","year":"2012","journal-title":"Lancet"},{"issue":"1","key":"2025033004023924900_qiae237-B8","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/1750-9378-5-5","article-title":"Impact of infection with human immunodeficiency virus-1 (HIV) on the risk of cancer among children in Malawi\u2014preliminary findings","volume":"5","author":"Mutalima","year":"2010","journal-title":"Infect Agent Cancer"},{"issue":"6","key":"2025033004023924900_qiae237-B9","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1111\/j.1365-2141.2011.08772.x","article-title":"Lymphomas in sub-Saharan Africa\u2013what can we learn and how can we help in improving diagnosis, managing patients and fostering translational research?","volume":"154","author":"Naresh","year":"2011","journal-title":"Br J Haematol"},{"issue":"12","key":"2025033004023924900_qiae237-B10","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1016\/S1470-2045(04)01650-X","article-title":"Is endemic Burkitt\u2019s lymphoma an alliance between three infections and a tumour promoter?","volume":"5","author":"van den Bosch","year":"2004","journal-title":"Lancet Oncol"},{"issue":"2","key":"2025033004023924900_qiae237-B11","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1182\/blood.V93.2.758","article-title":"What is Burkitt\u2019s lymphoma and when is it endemic?","volume":"93","author":"Wright","year":"1999","journal-title":"Blood"},{"issue":"8","key":"2025033004023924900_qiae237-B12","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1002\/ijc.24223","article-title":"Epstein-Barr virus and the pathogenesis of Burkitt\u2019s lymphoma: more questions than answers","volume":"124","author":"Bornkamm","year":"2009","journal-title":"Int J Cancer"},{"issue":"7335","key":"2025033004023924900_qiae237-B13","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1016\/S0140-6736(64)91524-7","article-title":"Virus particles in cultured lymphoblasts from Burkitt\u2019s lymphoma","volume":"1","author":"Epstein","year":"1964","journal-title":"Lancet"},{"issue":"3","key":"2025033004023924900_qiae237-B14","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1182\/blood-2018-04-844472","article-title":"How I treat Burkitt lymphoma in children, adolescents, and young adults in sub-Saharan Africa","volume":"132","author":"Gopal","year":"2018","journal-title":"Blood"},{"issue":"2","key":"2025033004023924900_qiae237-B15","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1136\/jcp.50.2.128","article-title":"Childhood non-Hodgkin lymphomas in the United Kingdom: findings from the UK Children\u2019s Cancer Study Group","volume":"50","author":"Wright","year":"1997","journal-title":"J Clin Pathol"},{"key":"2025033004023924900_qiae237-B16","doi-asserted-by":"publisher","first-page":"516047","DOI":"10.1155\/2010\/516047","article-title":"Burkitt lymphoma: pathogenesis and immune evasion","volume":"2010","author":"God","year":"2010","journal-title":"J Oncol"},{"issue":"27","key":"2025033004023924900_qiae237-B17","doi-asserted-by":"publisher","first-page":"2963","DOI":"10.1200\/JCO.2014.59.5827","article-title":"Non-Hodgkin lymphoma in children and adolescents: progress through effective collaboration, current knowledge, and challenges ahead","volume":"33","author":"Minard-Colin","year":"2015","journal-title":"J Clin Oncol"},{"issue":"1","key":"2025033004023924900_qiae237-B18","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1182\/asheducation-2015.1.514","article-title":"Hodgkin lymphoma in children and adolescents: improving the therapeutic index","volume":"2015","author":"Kelly","year":"2015","journal-title":"Hematology Am Soc Hematol Educ Program"},{"issue":"3","key":"2025033004023924900_qiae237-B19","doi-asserted-by":"publisher","first-page":"166","DOI":"10.5555\/afhs.2007.7.3.166","article-title":"Burkitt\u2019s lymphoma in Africa, a review of the epidemiology and etiology","volume":"7","author":"Orem","year":"2007","journal-title":"Afr Health Sci"},{"key":"2025033004023924900_qiae237-B20","doi-asserted-by":"publisher","first-page":"339","DOI":"10.2147\/CLEP.S35671","article-title":"Agreement between diagnoses of childhood lymphoma assigned in Uganda and by an international reference laboratory","volume":"4","author":"Orem","year":"2012","journal-title":"Clin Epidemiol"},{"key":"2025033004023924900_qiae237-B21","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.humpath.2018.05.020","article-title":"Epstein-Barr virus (EBV)-associated lymphoid proliferations, a 2018 update","volume":"79","author":"Rezk","year":"2018","journal-title":"Hum Pathol"},{"issue":"4","key":"2025033004023924900_qiae237-B22","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1002\/path.2410","article-title":"MYC translocation-negative classical Burkitt lymphoma cases: an alternative pathogenetic mechanism involving miRNA deregulation","volume":"216","author":"Leucci","year":"2008","journal-title":"J Pathol"},{"issue":"5","key":"2025033004023924900_qiae237-B23","doi-asserted-by":"publisher","first-page":"349","DOI":"10.2174\/1389202916666150707160147","article-title":"MicroRNAs in lymphoma: regulatory role and biomarker potential","volume":"16","author":"Fernandez-Mercado","year":"2015","journal-title":"Curr Genomics"},{"key":"2025033004023924900_qiae237-B24","doi-asserted-by":"publisher","first-page":"33","DOI":"10.2147\/BLCTT.S129618","article-title":"Current understanding of the role and regulation of miRNAs in Burkitt lymphoma","volume":"8","author":"Videtta","year":"2018","journal-title":"Blood Lymphat Cancer"},{"issue":"9","key":"2025033004023924900_qiae237-B25","doi-asserted-by":"publisher","first-page":"e12960","DOI":"10.1371\/journal.pone.0012960","article-title":"Alteration of microRNAs regulated by c-Myc in Burkitt lymphoma","volume":"5","author":"Onnis","year":"2010","journal-title":"PLoS One"},{"issue":"2","key":"2025033004023924900_qiae237-B26","doi-asserted-by":"publisher","first-page":"216","DOI":"10.4149\/neo_2023_221103N1079","article-title":"Hypoxia-induced miR-9 expression promotes ovarian cancer progression via activating PI3K\/AKT\/mTOR\/GSK3\u03b2 signaling pathway","volume":"70","author":"Zhu","year":"2023","journal-title":"Neoplasma"},{"issue":"1","key":"2025033004023924900_qiae237-B27","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s11658-019-0145-1","article-title":"Inhibition of miR-9-5p suppresses prostate cancer progress by targeting StarD13","volume":"24","author":"Chen","year":"2019","journal-title":"Cell Mol Biol Lett"},{"issue":"8","key":"2025033004023924900_qiae237-B28","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.3727\/096504016x14791715355957","article-title":"Upregulated miR-9-3p promotes cell growth and inhibits apoptosis in medullary thyroid carcinoma by targeting BLCAP","volume":"25","author":"Chen","year":"2017","journal-title":"Oncol Res"},{"issue":"9","key":"2025033004023924900_qiae237-B29","doi-asserted-by":"publisher","first-page":"7445","DOI":"10.1007\/s11033-023-08612-0","article-title":"Long non-coding RNA MIR22HG inhibits the proliferation and migration, and promotes apoptosis by targeting microRNA-9-3p\/SOCS1 axis in small cell lung cancer cells","volume":"50","author":"Wang","year":"2023","journal-title":"Mol Biol Rep"},{"issue":"12","key":"2025033004023924900_qiae237-B30","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1038\/leu.2011.156","article-title":"The different epidemiologic subtypes of Burkitt lymphoma share a homogenous micro RNA profile distinct from diffuse large B-cell lymphoma","volume":"25","author":"Lenze","year":"2011","journal-title":"Leukemia"},{"issue":"3","key":"2025033004023924900_qiae237-B31","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1038\/ncb2024","article-title":"miR-9, a MYC\/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis","volume":"12","author":"Ma","year":"2010","journal-title":"Nat Cell Biol"},{"issue":"32","key":"2025033004023924900_qiae237-B32","doi-asserted-by":"publisher","first-page":"6035","DOI":"10.1038\/s41388-019-0860-0","article-title":"MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC, WNT and AKT pathways","volume":"38","author":"Majem","year":"2019","journal-title":"Oncogene"},{"issue":"4","key":"2025033004023924900_qiae237-B33","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1007\/s12032-016-0749-5","article-title":"Micro-RNA (miRNA) profile in Hodgkin lymphoma: association between clinical and pathological variables","volume":"33","author":"Paydas","year":"2016","journal-title":"Med Oncol"},{"issue":"2","key":"2025033004023924900_qiae237-B34","first-page":"522","article-title":"MiR-654-5p attenuates breast cancer progression by targeting EPSTI1","volume":"6","author":"Tan","year":"2016","journal-title":"Am J Cancer Res"},{"issue":"56","key":"2025033004023924900_qiae237-B35","doi-asserted-by":"publisher","first-page":"5847","DOI":"10.18632\/oncotarget.27226","article-title":"GCN5 HAT inhibition reduces human Burkitt lymphoma cell survival through reduction of MYC target gene expression and impeding BCR signaling pathways","volume":"10","author":"Farria","year":"2019","journal-title":"Oncotarget"},{"issue":"24","key":"2025033004023924900_qiae237-B36","doi-asserted-by":"publisher","first-page":"4861","DOI":"10.1182\/blood-2012-12-475558","article-title":"Trends in survival of patients with Burkitt lymphoma\/leukemia in the USA: an analysis of 3691 cases","volume":"121","author":"Costa","year":"2013","journal-title":"Blood"},{"issue":"6","key":"2025033004023924900_qiae237-B37","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1002\/pbc.24416","article-title":"Children\u2019s Oncology Group\u2019s 2013 blueprint for research: non-Hodgkin lymphoma","volume":"60","author":"Bollard","year":"2013","journal-title":"Pediatr Blood Cancer"},{"issue":"6","key":"2025033004023924900_qiae237-B38","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1111\/j.1365-2141.2011.09024.x","article-title":"Risk factors and treatment of childhood and adolescent Burkitt lymphoma\/leukaemia","volume":"156","author":"Miles","year":"2012","journal-title":"Br J Haematol"},{"issue":"3","key":"2025033004023924900_qiae237-B39","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1002\/pbc.24407","article-title":"Practical recommendations for the management of children with endemic Burkitt lymphoma (BL) in a resource limited setting","volume":"60","author":"Hesseling","year":"2013","journal-title":"Pediatr Blood Cancer"},{"issue":"3","key":"2025033004023924900_qiae237-B40","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1097\/PAP.0b013e3182a92cde","article-title":"Burkitt lymphoma and MYC: what else is new?","volume":"21","author":"Said","year":"2014","journal-title":"Adv Anat Pathol"},{"issue":"6","key":"2025033004023924900_qiae237-B41","doi-asserted-by":"publisher","first-page":"431","DOI":"10.3109\/10428199209051025","article-title":"c-myc hypermutation in Burkitt\u2019s lymphoma","volume":"8","author":"Johnston","year":"1992","journal-title":"Leuk Lymphoma"},{"issue":"1","key":"2025033004023924900_qiae237-B42","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/1750-9378-9-12","article-title":"The Epstein Barr-encoded BART-6-3p microRNA affects regulation of cell growth and immuno response in Burkitt lymphoma","volume":"9","author":"Ambrosio","year":"2014","journal-title":"Infect Agent Cancer"},{"issue":"1","key":"2025033004023924900_qiae237-B43","doi-asserted-by":"publisher","first-page":"224","DOI":"10.18632\/oncotarget.4399","article-title":"Virus-encoded microRNA contributes to the molecular profile of EBV-positive Burkitt lymphomas","volume":"7","author":"Piccaluga","year":"2016","journal-title":"Oncotarget"},{"key":"2025033004023924900_qiae237-B44","doi-asserted-by":"publisher","first-page":"11","DOI":"10.2147\/AHMT.S94170","article-title":"Burkitt lymphoma in adolescents and young adults: management challenges","volume":"8","author":"Dozzo","year":"2017","journal-title":"Adolesc Health Med Ther"},{"issue":"3","key":"2025033004023924900_qiae237-B45","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1080\/15384047.2014.1002698","article-title":"Inauhzin(c) inactivates c-Myc independently of p53","volume":"16","author":"Jung","year":"2015","journal-title":"Cancer Biol Ther"},{"issue":"2","key":"2025033004023924900_qiae237-B46","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1007\/s00432-011-1093-y","article-title":"Histone deacetylase inhibitor potentiates chemotherapy-induced apoptosis through Bim upregulation in Burkitt\u2019s lymphoma cells","volume":"138","author":"dos Santos Ferreira","year":"2012","journal-title":"J Cancer Res Clin Oncol"},{"issue":"6","key":"2025033004023924900_qiae237-B47","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1007\/s00277-014-2021-4","article-title":"Histone deacetylase inhibitor prevents cell growth in Burkitt\u2019s lymphoma by regulating PI3K\/Akt pathways and leads to upregulation of miR-143, miR-145, and miR-101","volume":"93","author":"Ferreira","year":"2014","journal-title":"Ann Hematol"}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jleukbio\/advance-article-pdf\/doi\/10.1093\/jleuko\/qiae237\/60648942\/qiae237.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/117\/3\/qiae237\/60648942\/qiae237.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/117\/3\/qiae237\/60648942\/qiae237.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T19:43:48Z","timestamp":1743450228000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/doi\/10.1093\/jleuko\/qiae237\/7837031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,24]]},"references-count":47,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3,14]]}},"URL":"https:\/\/doi.org\/10.1093\/jleuko\/qiae237","relation":{},"ISSN":["1938-3673"],"issn-type":[{"type":"electronic","value":"1938-3673"}],"subject":[],"published-other":{"date-parts":[[2025,3]]},"published":{"date-parts":[[2024,10,24]]},"article-number":"qiae237"}}