{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T22:55:55Z","timestamp":1787180155300,"version":"build-2736575974"},"reference-count":64,"publisher":"SAGE Publications","issue":"16-18","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"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":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Ferroptosis is a nonapoptotic type of cell death characterized by an increase in lipid reactive oxygen species (ROS). Acute myeloid leukemia (AML)\u2013derived bone marrow mesenchymal stem cells (AML-BMSCs) support the progression and drug resistance of AML by secreting various bioactive substances, including exosomes. However, the role of BMSCs in regulating lipid metabolism and ferroptosis in AML remains unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Exosomes secreted by AML-BMSCs increased the expression of miR-196a-5p in AML cells. MiR-196a-5p promoted the proliferation of AML cells, reduced lipid ROS and ferroptosis, and was associated with poor prognosis in AML patients. Mechanistically, miR-196a-5p inhibited the expression level of neural precursor cell expressed developmentally down-regulated 4-like (NEDD4L). Co-immunoprecipitation (CO-IP) analysis showed that NEDD4L was bound to long-chain acyl-CoA synthetase (ACSL)3 and promoted ubiquitin-mediated degradation of ACSL3 protein. In addition, we also demonstrated that AML-BMSCs highly expressed Ras-associated binding protein 7A (RAB7A), which was associated with exosomal miR-196a-5p release. Importantly, cytarabine (Ara-C) activated the expression of RAB7A and promoted the secretion of exosomal miR-196a-5p, which weakened the ubiquitination of ACSL3 by NEDD4L, leading to ferroptosis inhibition and Ara-C resistance in AML.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>This is the first time that exosomes secreted by BMSCs (BMSCs-exos) have been linked to ferroptosis in AML cells, thereby expanding our understanding of the mechanism of drug resistance in AML cells. High miR-196a-5p expression reduced lipid ROS levels and ferroptosis in AML cells by inhibiting NEDD4L-mediated ubiquitination of ACSL3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      This study identified a new network through which BMSCs-exos regulate ferroptosis in AML cells. We combined BMSCs and AML cells to provide new ideas for drug research targeting exosome secretion and ferroptosis.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      42, 933\u2013953.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2024.0882","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T12:54:04Z","timestamp":1747659244000},"page":"933-953","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Exosomal miR-196a-5p Secreted by Bone Marrow Mesenchymal Stem Cells Inhibits Ferroptosis and Promotes Drug Resistance of Acute Myeloid Leukemia"],"prefix":"10.1177","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7528-359X","authenticated-orcid":false,"given":"Bingjie","family":"Fan","sequence":"first","affiliation":[{"name":"Key Laboratory of Hematological Disease Diagnostic and Treatment Centre, Affiliated Hospital of Guizhou Medical University, Guiyang, China."},{"name":"Department of Hematology, Affiliated Hospital of Guizhou Medical University, Guiyang, China."},{"name":"Department of Clinical Medical School, Guizhou Medical University, Guiyang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Hematological Disease Diagnostic and Treatment Centre, Affiliated Hospital of Guizhou Medical University, Guiyang, China."},{"name":"Department of Hematology, Affiliated Hospital of Guizhou Medical University, Guiyang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianzhen","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Hematological Disease Diagnostic and Treatment Centre, Affiliated Hospital of Guizhou Medical University, Guiyang, China."},{"name":"Department of Hematology, Affiliated Hospital of Guizhou Medical University, Guiyang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Hematological Disease Diagnostic and Treatment Centre, Affiliated Hospital of Guizhou Medical University, Guiyang, China."},{"name":"Department of Hematology, Affiliated Hospital of Guizhou Medical University, Guiyang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jishi","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Hematological Disease Diagnostic and Treatment Centre, Affiliated Hospital of Guizhou Medical University, Guiyang, China."},{"name":"Department of Hematology, Affiliated Hospital of Guizhou Medical University, Guiyang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"key":"e_1_3_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.04.013"},{"key":"e_1_3_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-017-9762-0"},{"key":"e_1_3_7_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009845"},{"key":"e_1_3_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60485-1"},{"key":"e_1_3_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1411-0"},{"key":"e_1_3_7_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-021-02327-7"},{"key":"e_1_3_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41570-020-00223-8"},{"key":"e_1_3_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022016362"},{"key":"e_1_3_7_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-0774"},{"key":"e_1_3_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042"},{"key":"e_1_3_7_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-08-733196"},{"key":"e_1_3_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(91)90192-6"},{"key":"e_1_3_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-2333(98)00005-8"},{"key":"e_1_3_7_15_1","doi-asserted-by":"publisher","DOI":"10.1863\/2\/aging.205565"},{"key":"e_1_3_7_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-16-0441"},{"key":"e_1_3_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.325"},{"key":"e_1_3_7_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02378-7"},{"key":"e_1_3_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-019-0493-x"},{"key":"e_1_3_7_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2016.1187366"},{"key":"e_1_3_7_21_1","doi-asserted-by":"publisher","DOI":"10.1525\/2\/embj.2019102301"},{"key":"e_1_3_7_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau6977"},{"key":"e_1_3_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.03.010"},{"key":"e_1_3_7_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.00475"},{"key":"e_1_3_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-021-00693-y"},{"key":"e_1_3_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.259"},{"key":"e_1_3_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2023.05.003"},{"key":"e_1_3_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00418-x"},{"key":"e_1_3_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03331-x"},{"key":"e_1_3_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-017-0053-8"},{"key":"e_1_3_7_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-021-00220-7"},{"key":"e_1_3_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2018.11.016"},{"key":"e_1_3_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0250-9"},{"key":"e_1_3_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-020-0245-2"},{"key":"e_1_3_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2010.08.002"},{"key":"e_1_3_7_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04464-1"},{"key":"e_1_3_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2023.100960"},{"key":"e_1_3_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2023.100936"},{"key":"e_1_3_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2021.174397"},{"key":"e_1_3_7_40_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201211138"},{"key":"e_1_3_7_41_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66517"},{"key":"e_1_3_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2013.12.005"},{"key":"e_1_3_7_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06814-3"},{"key":"e_1_3_7_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003661"},{"key":"e_1_3_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202307695"},{"key":"e_1_3_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2012.02.001"},{"key":"e_1_3_7_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-024-01685-9"},{"key":"e_1_3_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.021"},{"key":"e_1_3_7_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-00441-1"},{"key":"e_1_3_7_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2623-z"},{"key":"e_1_3_7_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1596"},{"key":"e_1_3_7_52_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202112032"},{"key":"e_1_3_7_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1170-y"},{"key":"e_1_3_7_54_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-03-562439"},{"key":"e_1_3_7_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01341-7"},{"key":"e_1_3_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.11.010"},{"key":"e_1_3_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2024.01.005"},{"key":"e_1_3_7_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-021-01307-9"},{"key":"e_1_3_7_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10565-024-09866-5"},{"key":"e_1_3_7_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06836-x"},{"key":"e_1_3_7_61_1","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/4024887"},{"key":"e_1_3_7_62_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.687975"},{"key":"e_1_3_7_63_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01168-8"},{"key":"e_1_3_7_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202105811"},{"key":"e_1_3_7_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.261"}],"container-title":["Antioxidants &amp; Redox Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/ars.2024.0882","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/ars.2024.0882","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/ars.2024.0882","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:56:04Z","timestamp":1777377364000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/ars.2024.0882"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":64,"journal-issue":{"issue":"16-18","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1089\/ars.2024.0882"],"URL":"https:\/\/doi.org\/10.1089\/ars.2024.0882","relation":{},"ISSN":["1523-0864","1557-7716"],"issn-type":[{"value":"1523-0864","type":"print"},{"value":"1557-7716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]}}}