{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T02:22:37Z","timestamp":1789438957050,"version":"build-2803163510"},"reference-count":54,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Institutes of Health Research","award":["MOP-111074"],"award-info":[{"award-number":["MOP-111074"]}]},{"name":"Natural Sciences and Engineering Research Council of Canada","award":["MOP-111074"],"award-info":[{"award-number":["MOP-111074"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Angiopoietin-1 (Ang-1) and its receptor Tie-2 promote vascular integrity and angiogenesis. MicroRNAs (miRNAs) are involved in the regulation of many cellular functions, including endothelial cell (EC) survival, proliferation, and differentiation. Several reports indicate that these effects of miRNAs on EC functions are mediated through the modulation of angiogenesis factor signaling including that of vascular endothelial growth factor (VEGF). To date, very little is known about the roles played by miRNAs in the signaling and angiogenesis promoted by the Ang-1\u2013Tie-2 receptor axis. Our high-throughput screening of miRNAs regulated by Ang-1 exposure in human umbilical vein endothelial cells (HUVECs) has identified miR-1233-3p as a mature miRNA whose cellular levels are significantly downregulated in response to Ang-1 exposure. The expression of miR-1233-3p in these cells is also downregulated by other angiogenesis factors including VEGF, fibroblast growth factor 2 (FGF-2), transforming growth factor \u03b2 (TGF\u03b2), and angiopoietin-2 (Ang-2). The overexpression of miR-1233-3p in HUVECs using specific mimics significantly attenuated cell survival, migration, and capillary-like tube formation, and promoted apoptosis. Moreover, miR-1233-3p overexpression resulted in reversal of the anti-apoptotic, pro-migration, and pro-differentiation effects of Ang-1. Biotinylated miRNA pull-down assays showed that p53 and DNA damage-regulated 1 (PDRG1) is a direct target of miR-1233-3p in HUVECs. The exposure of HUVECs to Ang-1, angiopoietin-2 (Ang-2), fibroblast growth factor 2 (FGF2), vascular endothelial growth factor (VEGF), or transforming growth factor \u03b2 (TGF\u03b2) triggers the regulation of PDRG1 expression. This study highlights that miR-1233-3p exerts inhibitory effects on Ang-1-induced survival, migration, and the differentiation of cultured ECs.<\/jats:p>","DOI":"10.3390\/cells14020075","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T09:30:45Z","timestamp":1736328645000},"page":"75","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["miR-1233-3p Inhibits Angiopoietin-1-Induced Endothelial Cell Survival, Migration, and Differentiation"],"prefix":"10.3390","volume":"14","author":[{"given":"Veronica","family":"Sanchez","sequence":"first","affiliation":[{"name":"Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada"},{"name":"Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, 1001 D\u00e9carie Blvd., Montreal, QC H4A 3J1, Canada"},{"name":"Department of Critical Care, McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Harel","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada"},{"name":"Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, 1001 D\u00e9carie Blvd., Montreal, QC H4A 3J1, Canada"},{"name":"Department of Critical Care, McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anas Khalid","family":"Sa\u2019ub","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada"},{"name":"Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, 1001 D\u00e9carie Blvd., Montreal, QC H4A 3J1, Canada"},{"name":"Department of Critical Care, McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Mayaki","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada"},{"name":"Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, 1001 D\u00e9carie Blvd., Montreal, QC H4A 3J1, Canada"},{"name":"Department of Critical Care, McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabah N. A.","family":"Hussain","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada"},{"name":"Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, 1001 D\u00e9carie Blvd., Montreal, QC H4A 3J1, Canada"},{"name":"Department of Critical Care, McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1161\/CIRCRESAHA.120.316851","article-title":"Basic and therapeutic aspects of angiogenesis updated","volume":"127","author":"Eelen","year":"2020","journal-title":"Circ. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.canlet.2012.08.018","article-title":"Angiopoietins in angiogenesis","volume":"328","author":"Fagiani","year":"2013","journal-title":"Cancer Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1096\/fj.02-0698fje","article-title":"Angiopoietin-1 activates both anti- and proapoptotic mitogen-activated protein kinases","volume":"17","author":"Harfouche","year":"2003","journal-title":"FASEB J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/S0092-8674(00)81813-9","article-title":"Requisite role of Angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis","volume":"87","author":"Suri","year":"1996","journal-title":"Cell"},{"key":"ref_5","first-page":"159","article-title":"Functions of Tie1 and Tie2 receptor tyrosine kinases in vascular development","volume":"237","author":"Partanen","year":"1999","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1128\/MCB.25.11.4693-4702.2005","article-title":"Selective role of a distinct tyrosine residue on Tie2 in heart development and early hematopoiesis","volume":"25","author":"Tachibana","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1161\/01.RES.0000218275.54089.12","article-title":"Signaling and functions of angiopoietin-1 in vascular protection","volume":"98","author":"Brindle","year":"2006","journal-title":"Circ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/74725","article-title":"Angiopoietin-1 protects the adult vasculature against plasma leakage","volume":"6","author":"Thurston","year":"2000","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.tox.2007.12.011","article-title":"Potential target sites to modulate vascular endothelial dysfunction: Current perspectives and future directions","volume":"245","author":"Balakumar","year":"2008","journal-title":"Toxicology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1007\/s11010-023-04919-5","article-title":"Non-coding RNAs and angiogenesis in cardiovascular diseases: A comprehensive review","volume":"479","author":"Zhang","year":"2024","journal-title":"Mol. Cell Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.semcdb.2021.07.007","article-title":"Non-coding RNAs in cardiac regeneration: Mechanism of action and therapeutic potential","volume":"118","author":"Wang","year":"2021","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nature03049","article-title":"Processing of primary microRNAs by the Microprocessor complex","volume":"432","author":"Denli","year":"2004","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nature03120","article-title":"The Microprocessor complex mediates the genesis of microRNAs","volume":"432","author":"Gregory","year":"2004","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1261\/rna.5167604","article-title":"Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs","volume":"10","author":"Bohnsack","year":"2004","journal-title":"RNA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/nature03868","article-title":"TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing","volume":"436","author":"Chendrimada","year":"2005","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1161\/CIRCRESAHA.111.247445","article-title":"MicroRNAs in Vascular and Metabolic Disease","volume":"110","author":"Zampetaki","year":"2012","journal-title":"Circ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e48095","DOI":"10.7554\/eLife.48095","article-title":"A regulatory microRNA network controls endothelial cell phenotypic switch during sprouting angiogenesis","volume":"9","author":"Rosano","year":"2020","journal-title":"eLife"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e22412","DOI":"10.1096\/fj.202101987R","article-title":"The hypoxia-induced changes in miRNA-mRNA in RNA-induced silencing complexc and HIF-2 induced miRNA in human endothelial cells","volume":"36","author":"Moszynska","year":"2022","journal-title":"FASEB J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"13027","DOI":"10.1073\/pnas.0805038105","article-title":"Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis","volume":"105","author":"Sutherland","year":"2008","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"H1519","DOI":"10.1152\/ajpheart.01080.2010","article-title":"microRNA-210 is upregulated in hypoxic cardiomyocytes through Akt- and p53-dependent pathways and exerts cytoprotective effects","volume":"301","author":"Mutharasan","year":"2011","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.phrs.2018.11.010","article-title":"Negative regulation of angiogenesis by novel micro RNAs","volume":"139","author":"Sanchez","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Qureshi, R., and Sacan, A. (2013). A novel method for the normalization of microRNA RT-PCR data. BMC Med. Genom., 6.","DOI":"10.1186\/1755-8794-6-S1-S14"},{"key":"ref_23","unstructured":"Carpentier, G., Martinelli, M., Courty, J., and Cascone, I. (2024, November 17). The 4th ImageJ User and Developer Conference Proceedings. 2012, 198\u2013201. ISBN: 2-919941-18-6. Available online: http:\/\/image.bio.methods.free.fr\/ImageJ\/IMG\/pdf\/angiogenesisanalyzer.pdf."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/nature07666","article-title":"Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex","volume":"456","author":"Wang","year":"2008","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cloonan, N., Wani, S., Xu, Q., Gu, J., Lea, K., Heater, S., Barbacioru, C., Steptoe, A.L., Martin, H.C., and Nourbakhsh, E. (2011). MicroRNAs and their isomiRs function cooperatively to target common biological pathways. Gen. Biol., 12c.","DOI":"10.1186\/gb-2011-12-12-r126"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ymeth.2007.04.007","article-title":"Isolation of microRNA targets using biotinylated synthetic microRNAs","volume":"43","author":"Orom","year":"2007","journal-title":"Methods"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Guduric-Fuchs, J., O\u2019Connor, A., Camp, B., O\u2019Neill, C.L., Medina, R.J., and Simpson, D.A. (2012). Selective extracellular vesicle-mediated export of an overlapping set of microRNAs from multiple cell types. BMC Genom., 13.","DOI":"10.1186\/1471-2164-13-357"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1007\/s12012-022-09740-y","article-title":"Exosomes derived from senescent endothelial cells contain distinct pro-angiogenic miRNAs and proteins","volume":"22","author":"Shaban","year":"2022","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1183\/09031936.00029610","article-title":"Vesicle-related microRNAs in plasma of nonsmall cell lung cancer patients and correlation with survival","volume":"37","author":"Silva","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1101\/gad.177774.111","article-title":"Intronic miR-26b controls neuronal differentiation by repressing its host transcript, ctdsp2","volume":"26","author":"Dill","year":"2012","journal-title":"Genes Dev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14082","DOI":"10.1073\/pnas.0804597105","article-title":"Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesis","volume":"105","author":"Suarez","year":"2008","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.ccr.2008.10.005","article-title":"miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells","volume":"14","author":"Wuerdinger","year":"2008","journal-title":"Cancer Cell."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Smits, M., Mir, S.E., A Nilsson, R.J., van der Stoop, P.M., Niers, J.M., Marquez, V.E., Cloos, J., Breakefield, X.O., Krichevsky, A.M., and Noske, D.P. (2011). Down-Regulation of miR-101 in endothelial cells promotes blood vessel formation through reduced repression of EZH2. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016282"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1093\/cvr\/cvv120","article-title":"Angiopoietin-1 inhibits toll-like receptor 4 signalling in cultured endothelial cells: Role of miR-146b-5p","volume":"106","author":"Echavarria","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/ncb2210","article-title":"MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins","volume":"13","author":"Vickers","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhang, S., Yang, Y., Lv, X., Liu, W., Zhu, S., Wang, Y., and Xu, H. (2023). Unraveling the intricate roles of exosomes in cardiovascular diseases: A comprehensive review of physiological significance and pathological implications. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242115677"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1161\/CIRCRESAHA.110.226456","article-title":"Microparticles protagonists of a novel communication network for intercellular information exchange","volume":"107","author":"Mause","year":"2010","journal-title":"Cir. Res."},{"key":"ref_38","first-page":"9121","article-title":"Expression of miRNA-1233 in placenta from patients with hypertensive disorder complicating pregnancy and its role in disease pathogenesis","volume":"8","author":"Zhong","year":"2015","journal-title":"Internat. J. Clin. Exp. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"686","DOI":"10.3892\/br.2016.779","article-title":"Dysregulated circulating miRNAs in preeclampsia","volume":"5","author":"Munaut","year":"2016","journal-title":"Biomed. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wulfken, L.M., Moritz, R., Ohlmann, C., Holdenrieder, S., Jung, V., Becker, F., Herrmann, E., Walgenbach-Br\u00fcnagel, G., von Ruecker, A., and Muller, S.C. (2011). MicroRNAs in renal cell carcinoma: Diagnostic implications of serum miR-1233 levels. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025787"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4862","DOI":"10.1074\/jbc.M305190200","article-title":"The homeobox transcription factor Hox D3 promotes integrin alpha(5)beta(1) expression and function during angiogenesis","volume":"279","author":"Boudreau","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1242\/jcs.02399","article-title":"HOXA3 induces cell migration in endothelial and epithelial cells promoting angiogenesis and wound repair","volume":"118","author":"Mace","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1083\/jcb.148.2.343","article-title":"Homeobox B3 promotes capillary morphogenesis and angiogenesis","volume":"148","author":"Myers","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1016\/S0002-9440(10)64488-4","article-title":"Sustained expression of homeobox D10 inhibits angiogenesis","volume":"161","author":"Myers","year":"2002","journal-title":"Am. J. Path."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/35016125","article-title":"Compromised HOXA5 function can limit p53 expression in human breast tumours","volume":"405","author":"Raman","year":"2000","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s11033-007-9171-6","article-title":"HOX gene analysis of endothelial cell differentiation in human bone marrow-derived mesenchymal stem cells","volume":"36","author":"Chung","year":"2009","journal-title":"Mol. Biol. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.canlet.2012.11.051","article-title":"HoxB3 promotes prostate cancer cell progression by transactivating CDCA3","volume":"330","author":"Chen","year":"2013","journal-title":"Cancer Lett."},{"key":"ref_48","first-page":"1551","article-title":"Deregulation of MicroRNA-375 inhibits cancer proliferation migration and chemosensitivity in pancreatic cancer through the association of HOXB3","volume":"8","author":"Yang","year":"2016","journal-title":"Am. J. Trans. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7247","DOI":"10.1038\/sj.onc.1207010","article-title":"Cloning and characterization of a novel gene PDRG that is differentially regulated by p53 and ultraviolet radiation","volume":"22","author":"Luo","year":"2003","journal-title":"Oncogene"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.molcel.2010.08.023","article-title":"HSP90 and its R2TP\/Prefoldin-like cochaperone are involved in the cytoplasmic assembly of RNA polymerase II","volume":"39","author":"Boulon","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Mita, P., Savas, J.N., Ha, S., Djouder, N., Yates III, J.R., and Logan, S.K. (2013). Analysis of URI nuclear interaction with RPB5 and components of the R2TP\/prefoldin-like complex. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063879"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"567","DOI":"10.4161\/cbt.11.6.14412","article-title":"PDRG1, a novel tumor marker for multiple malignancies that is selectively regulated by genotoxic stress","volume":"11","author":"Jiang","year":"2011","journal-title":"Cancer Biol. Therap."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1111\/cas.15214","article-title":"PDRG1 promotes the proliferation and migration of GBM cells by MEK\/ERK\/CD44 pathway","volume":"113","author":"Sun","year":"2022","journal-title":"Cancer Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"112924","DOI":"10.1016\/j.yexcr.2021.112924","article-title":"PDRG1 predicts poor prognosis and facilitates the proliferation and metastasis of colorectal cancer","volume":"409","author":"Xu","year":"2021","journal-title":"Exp. Cell. Res."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/2\/75\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:24:54Z","timestamp":1759919094000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/2\/75"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,8]]},"references-count":54,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["cells14020075"],"URL":"https:\/\/doi.org\/10.3390\/cells14020075","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,8]]}}}