{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:06:24Z","timestamp":1777388784615,"version":"3.51.4"},"reference-count":28,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific research project of the Education Department of Liaoning Province"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>In this study, we aimed to investigate the effect of p62 on angiogenesis and microRNA (miRNA) expression profiles in acute myeloid leukemia (AML) exosomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An Exiqon v19.0 microRNA MicroArray was used to profile miRNAs in exosomes derived from parental and p62-knockdown U937 cells. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to predict the biological functions and potential mechanisms of differentially expressed miRNAs in AML exosomes. Endothelial cell tube formation assays using human umbilical vein endothelial cells (HUVECs) were performed to investigate the effect of AML exosomes on angiogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We demonstrated that 2,080 miRNAs were expressed in exosomes derived from our cultured cell samples, of which 215 and 208 miRNAs were upregulated and downregulated, respectively, in p62-knockdown U937 cells (fold change \u2265 2,\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05). GO analysis indicated that miRNAs were most enriched in the intercellular pathways. Biological process analysis revealed that 1460 biological processes were associated with downregulated transcripts, including 19 pathways related to vesicles, and 1,515 pathways were upregulated, including 8 pathways related to vesicles. Molecular function analysis indicated that protein binding, transcription regulator activity, and DNA-binding transcription factor activity were enriched (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05). Pathway analysis indicated that 84 pathways corresponded to upregulated transcripts, and 55 pathways corresponded to downregulated transcripts (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05). We also found that exosomes derived from U937 cells promoted angiogenesis in HUVECs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data suggest that exosomal miRNAs may play important roles in the pathogenesis of AML, which may be treated by p62 knockdown with exosomal miRNAs to inhibit angiogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.13498","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T04:21:07Z","timestamp":1658463667000},"page":"e13498","source":"Crossref","is-referenced-by-count":4,"title":["Analysis of microRNA expression profiles in exosomes derived from acute myeloid leukemia by p62 knockdown and effect on angiogenesis"],"prefix":"10.7717","volume":"10","author":[{"given":"Chuan","family":"Li","sequence":"first","affiliation":[{"name":"Hematology Department, Shengjing Hospital of China Medical University, Shenyang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyi","family":"Long","sequence":"additional","affiliation":[{"name":"Hematology Department, Shengjing Hospital of China Medical University, Shenyang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiqi","family":"Liang","sequence":"additional","affiliation":[{"name":"Hematology Department, The First Affiliated Hospital of Suzhou University, Suzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuogang","family":"Liu","sequence":"additional","affiliation":[{"name":"Hematology Department, Shengjing Hospital of China Medical University, Shenyang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Hematology Department, Shengjing Hospital of China Medical University, Shenyang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Hu","sequence":"additional","affiliation":[{"name":"Hematology Department, Shengjing Hospital of China Medical University, Shenyang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"10.7717\/peerj.13498\/ref-1","doi-asserted-by":"publisher","first-page":"e05005","DOI":"10.7554\/eLife.05005","article-title":"Predicting effective microRNA target sites in mammalian mRNAs","volume":"4","author":"Agarwal","year":"2015","journal-title":"Elife"},{"key":"10.7717\/peerj.13498\/ref-2","doi-asserted-by":"publisher","first-page":"16885","DOI":"10.1002\/jcp.28374","article-title":"Tumor-derived exosomes: implication in angiogenesis and antiangiogenesis cancer therapy","volume":"234","author":"Aslan","year":"2019","journal-title":"Journal of Cellular Physiology"},{"key":"10.7717\/peerj.13498\/ref-3","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1200\/JCO.2010.30.1820","article-title":"Therapeutic advances in acute myeloid leukemia","volume":"29","author":"Burnett","year":"2011","journal-title":"Journal of Clinical Oncology"},{"key":"10.7717\/peerj.13498\/ref-4","doi-asserted-by":"publisher","first-page":"D127","DOI":"10.1093\/nar\/gkz757","article-title":"miRDB: an online database for prediction of functional microRNA targets","volume":"48","author":"Chen","year":"2020","journal-title":"Nucleic Acids Research"},{"key":"10.7717\/peerj.13498\/ref-5","doi-asserted-by":"publisher","first-page":"e441","DOI":"10.1038\/bcj.2016.50","article-title":"Acute myeloid leukemia: a comprehensive review and 2016 update","volume":"6","author":"De Kouchkovsky","year":"2016","journal-title":"Blood Cancer Journal"},{"key":"10.7717\/peerj.13498\/ref-6","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1179\/1607845413Y.0000000139","article-title":"Angiogenesis and acute myeloid leukemia","volume":"19","author":"Haouas","year":"2014","journal-title":"Hematology"},{"key":"10.7717\/peerj.13498\/ref-7","doi-asserted-by":"publisher","first-page":"ra88","DOI":"10.1126\/scisignal.aaf2797","article-title":"AML suppresses hematopoiesis by releasing exosomes that contain microRNAs targeting c-MYB","volume":"9","author":"Hornick","year":"2016","journal-title":"Science Signaling"},{"key":"10.7717\/peerj.13498\/ref-8","doi-asserted-by":"publisher","first-page":"22847","DOI":"10.1074\/jbc.M802182200","article-title":"Structural basis for sorting mechanism of p62 in selective autophagy","volume":"283","author":"Ichimura","year":"2008","journal-title":"Journal of Biological Chemistry"},{"key":"10.7717\/peerj.13498\/ref-9","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/s41419-018-0570-5","article-title":"GATA4 regulates angiogenesis and persistence of inflammation in rheumatoid arthritis","volume":"9","author":"Jia","year":"2018","journal-title":"Cell Death & Disease"},{"key":"10.7717\/peerj.13498\/ref-10","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.phrs.2012.07.004","article-title":"p62\/SQSTM1\/A170: physiology and pathology","volume":"66","author":"Komatsu","year":"2012","journal-title":"Pharmacological Research"},{"key":"10.7717\/peerj.13498\/ref-11","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1001\/jamaneurol.2013.3849","article-title":"SQSTM1 mutations in French patients with frontotemporal dementia or frontotemporal dementia with amyotrophic lateral sclerosis","volume":"70","author":"Le Ber","year":"2013","journal-title":"JAMA Neurology"},{"key":"10.7717\/peerj.13498\/ref-12","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1111\/ejh.12719","article-title":"Loss of c-Kit and bone marrow failure upon conditional removal of the GATA-2 C-terminal zinc finger domain in adult mice","volume":"97","author":"Li","year":"2016","journal-title":"European Journal of Haematology"},{"key":"10.7717\/peerj.13498\/ref-13","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1002\/jcp.27067","article-title":"Wogonoside impedes the progression of acute myeloid leukemia through inhibiting bone marrow angiogenesis","volume":"234","author":"Lin","year":"2019","journal-title":"Journal of Cellular Physiology"},{"key":"10.7717\/peerj.13498\/ref-14","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s11658-016-0031-z","article-title":"p62 links the autophagy pathway and the ubiqutin-proteasome system upon ubiquitinated protein degradation","volume":"21","author":"Liu","year":"2016","journal-title":"Cellular & Molecular Biology Letters"},{"key":"10.7717\/peerj.13498\/ref-15","doi-asserted-by":"publisher","first-page":"22426","DOI":"10.1074\/jbc.M110.149252","article-title":"Dynamics of the degradation of ubiquitinated proteins by proteasomes and autophagy: association with sequestosome 1\/p62","volume":"286","author":"Myeku","year":"2011","journal-title":"Journal of Biological Chemistry"},{"key":"10.7717\/peerj.13498\/ref-16","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1074\/mcp.M116.058321","article-title":"Hyper-phosphorylation of sequestosome-1 distinguishes resistance to cisplatin in patient derived high grade serous ovarian cancer cells","volume":"16","author":"Nguyen","year":"2017","journal-title":"Molecular & Cellular Proteomics"},{"key":"10.7717\/peerj.13498\/ref-17","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1182\/blood-2018-02-833475","article-title":"Loss of the selective autophagy receptor p62 impairs murine myeloid leukemia progression and mitophagy","volume":"133","author":"Nguyen","year":"2019","journal-title":"Blood"},{"key":"10.7717\/peerj.13498\/ref-18","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1097\/MOH.0000000000000235","article-title":"Exosomes promote bone marrow angiogenesis in hematologic neoplasia: the role of hypoxia","volume":"23","author":"Ohyashiki","year":"2016","journal-title":"Current Opinion in Hematology"},{"key":"10.7717\/peerj.13498\/ref-19","doi-asserted-by":"publisher","first-page":"24131","DOI":"10.1074\/jbc.M702824200","article-title":"p62\/SQSTM1 binds directly to Atg8\/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy","volume":"282","author":"Pankiv","year":"2007","journal-title":"Journal of Biological Chemistry"},{"key":"10.7717\/peerj.13498\/ref-20","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1056\/NEJMoa1112304","article-title":"Prognostic relevance of integrated genetic profiling in acute myeloid leukemia","volume":"366","author":"Patel","year":"2012","journal-title":"New England Journal of Medicine"},{"key":"10.7717\/peerj.13498\/ref-21","doi-asserted-by":"publisher","first-page":"12030","DOI":"10.1038\/ncomms12030","article-title":"p62\/Sqstm1 promotes malignancy of HCV-positive hepatocellular carcinoma through Nrf2-dependent metabolic reprogramming","volume":"7","author":"Saito","year":"2016","journal-title":"Nature Communications"},{"key":"10.7717\/peerj.13498\/ref-22","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/S0140-6736(18)31041-9","article-title":"Acute myeloid leukaemia","volume":"392","author":"Short","year":"2018","journal-title":"Lancet"},{"key":"10.7717\/peerj.13498\/ref-23","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1038\/ncb1800","article-title":"Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers","volume":"10","author":"Skog","year":"2008","journal-title":"Nature Cell Biology"},{"issue":"10","key":"10.7717\/peerj.13498\/ref-24","doi-asserted-by":"publisher","first-page":"3198","DOI":"10.3390\/ijms19103198","article-title":"Targeting oncogenic signaling in mutant FLT3 acute myeloid leukemia: the path to least resistance","volume":"19","author":"Staudt","year":"2018","journal-title":"International Journal of Molecular Sciences"},{"key":"10.7717\/peerj.13498\/ref-25","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.bbrc.2010.04.019","article-title":"Sphingosine-1-phosphate induces human endothelial VEGF and MMP-2 production via transcription factor ZNF580: novel insights into angiogenesis","volume":"395","author":"Sun","year":"2010","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"10.7717\/peerj.13498\/ref-26","doi-asserted-by":"publisher","first-page":"1852","DOI":"10.1038\/cdd.2014.102","article-title":"p62\/SQSTM1 upregulation constitutes a survival mechanism that occurs during granulocytic differentiation of acute myeloid leukemia cells","volume":"21","author":"Trocoli","year":"2014","journal-title":"Cell Death & Differentiation"},{"key":"10.7717\/peerj.13498\/ref-27","doi-asserted-by":"publisher","first-page":"10602","DOI":"10.1002\/jcp.27735","article-title":"Exosomes derived from acute myeloid leukemia cells promote chemoresistance by enhancing glycolysis-mediated vascular remodeling","volume":"234","author":"Wang","year":"2019","journal-title":"Journal of Cellular Physiology"},{"key":"10.7717\/peerj.13498\/ref-28","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1038\/nm.3733","article-title":"Age-related mutations associated with clonal hematopoietic expansion and malignancies","volume":"20","author":"Xie","year":"2014","journal-title":"Nature Medicine"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/13498.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/13498.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/13498.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/13498.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T04:22:02Z","timestamp":1658463722000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/13498"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,22]]},"references-count":28,"alternative-id":["10.7717\/peerj.13498"],"URL":"https:\/\/doi.org\/10.7717\/peerj.13498","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.7287\/peerj.13498v0.2\/reviews\/1","asserted-by":"object"},{"id-type":"doi","id":"10.7287\/peerj.13498v0.2\/reviews\/2","asserted-by":"object"},{"id-type":"doi","id":"10.7287\/peerj.13498v0.1\/reviews\/1","asserted-by":"object"},{"id-type":"doi","id":"10.7287\/peerj.13498v0.1\/reviews\/2","asserted-by":"object"}]},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,22]]},"article-number":"e13498"}}