{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:10:48Z","timestamp":1783577448542,"version":"3.55.0"},"reference-count":43,"publisher":"Portland Press Ltd.","issue":"6","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":603,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,12,22]]},"abstract":"<jats:p>It is known that the guanine-rich strands in proto-oncogene promoters can fold into G-quadruplex structures to regulate gene expression. An intramolecular parallel G-quadruplex has been identified in MET promoter. It acts as a repressor in regulating MET expression. However, the full guanine-rich region in MET promoter forms a hybrid parallel\/antiparallel G-quadruplex structure under physiological conditions, which means there are some antiparallel and hybrid parallel\/antiparallel G-quadruplex structures in this region. In the present study, our data indicate that g3-5 truncation adopts an intramolecular hybrid parallel\/antiparallel G-quadruplex under physiological conditions in vitro. The g3-5 G-quadruplex structure significantly stops polymerization by Klenow fragment in K+ buffer. Furthermore, the results of circular dichroism (CD) spectra and polymerase stop assay directly demonstrate that the G-quadruplex structure in g3-5 fragment can be stabilized by the G-quadruplex ligand TMPyP4 (5,10,15,20-tetra-(N-methyl-4-pyridyl) porphine). But the dual luciferase assay indicates TMPyP4 has no effect on the formation of g3-5 G-quadruplex in HepG2 cells. The findings in the present study will enrich our understanding of the G-quadruplex formation in proto-oncogene promoters and the mechanisms of gene expression regulation.<\/jats:p>","DOI":"10.1042\/bsr20171128","type":"journal-article","created":{"date-parts":[[2017,10,23]],"date-time":"2017-10-23T15:47:27Z","timestamp":1508773647000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A novel G-quadruplex motif in the Human <i>MET<\/i> promoter region"],"prefix":"10.1042","volume":"37","author":[{"given":"Jing","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, Liaoning 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Dalian Municipal Central Hospital, Dalian, Liaoning 116033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Dong","sequence":"additional","affiliation":[{"name":"Library of China Medical University, Shenyang, Liaoning 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, Liaoning 110122, China"},{"name":"Department of Physiology, Jinzhou Medical University, Liaoning 121001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjin","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, Liaoning 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifu","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, Liaoning 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2017,11,29]]},"reference":[{"key":"2021111619022395100_B1","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.1158\/1078-0432.CCR-06-0818","article-title":"Targeting the c-Met signaling pathway in cancer","volume":"12","author":"Peruzzi","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"2021111619022395100_B2","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1038\/nrm1261","article-title":"Met, metastasis, motility and more","volume":"4","author":"Birchmeier","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2021111619022395100_B3","doi-asserted-by":"crossref","first-page":"833","DOI":"10.5483\/BMBRep.2008.41.12.833","article-title":"The hepatocyte growth factor\/c-Met signaling pathway as a therapeutic target to inhibit angiogenesis","volume":"41","author":"You","year":"2008","journal-title":"BMB Rep."},{"key":"2021111619022395100_B4","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.lungcan.2008.06.011","article-title":"MET as a target for treatment of chest tumors","volume":"63","author":"Cipriani","year":"2009","journal-title":"Lung Cancer"},{"key":"2021111619022395100_B5","doi-asserted-by":"crossref","first-page":"20932","DOI":"10.1073\/pnas.0710370104","article-title":"MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib","volume":"104","author":"Bean","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021111619022395100_B6","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s12094-010-0501-0","article-title":"C-MET as a new therapeutic target for the development of novel anticancer drugs","volume":"12","author":"Ca\u00f1adas","year":"2010","journal-title":"Clin. Transl. Oncol."},{"key":"2021111619022395100_B7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2004.09.044","article-title":"c-Met as a target for human cancer and characterization of inhibitors for therapeutic intervention","volume":"225","author":"Christensen","year":"2005","journal-title":"Cancer Lett."},{"key":"2021111619022395100_B8","doi-asserted-by":"crossref","first-page":"5402","DOI":"10.1093\/nar\/gkl655","article-title":"Quadruplex DNA: sequence, topology and structure","volume":"34","author":"Burge","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"2021111619022395100_B9","doi-asserted-by":"crossref","first-page":"7429","DOI":"10.1093\/nar\/gkm711","article-title":"Human telomere, oncogenic promoter and 5\u2032-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics","volume":"35","author":"Patel","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2021111619022395100_B10","doi-asserted-by":"crossref","first-page":"5799","DOI":"10.1093\/nar\/gkm609","article-title":"Sequence occurrence and structural uniqueness of a G-quadruplex in the human c-kit promoter","volume":"35","author":"Todd","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2021111619022395100_B11","doi-asserted-by":"crossref","first-page":"11593","DOI":"10.1073\/pnas.182256799","article-title":"Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription","volume":"99","author":"Siddiqui-Jain","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021111619022395100_B12","doi-asserted-by":"crossref","first-page":"6070","DOI":"10.1093\/nar\/gki917","article-title":"Facilitation of a structural transition in the polypurine\/polypyrimidine tract within the proximal promoter region of the human VEGF gene by the presence of potassium and G-quadruplex-interactive agents","volume":"33","author":"Sun","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"2021111619022395100_B13","doi-asserted-by":"crossref","first-page":"5404","DOI":"10.1021\/ja0563861","article-title":"Deconvoluting the structural and drug-recognition complexity of the G-quadruplex-forming region upstream of the bcl-2 P1 promoter","volume":"128","author":"Dexheimer","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"2021111619022395100_B14","doi-asserted-by":"crossref","first-page":"16341","DOI":"10.1021\/bi051618u","article-title":"Evidence for the presence of a guanine quadruplex forming region within a polypurine tract of the hypoxia inducible factor 1\u03b1 promoter","volume":"44","author":"De Armond","year":"2005","journal-title":"Biochemistry"},{"key":"2021111619022395100_B15","doi-asserted-by":"crossref","first-page":"10220","DOI":"10.1021\/ja072185g","article-title":"Formation of pseudosymmetrical G-quadruplex and i-motif structures in the proximal promoter region of the RET oncogene","volume":"129","author":"Guo","year":"2007","journal-title":"J. Am. Chem. Soc."},{"key":"2021111619022395100_B16","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1093\/nar\/gkl286","article-title":"G-quadruplex formation within the promoter of the KRAS proto-oncogene and its effect on transcription","volume":"34","author":"Cogoi","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"2021111619022395100_B17","doi-asserted-by":"crossref","first-page":"7698","DOI":"10.1093\/nar\/gkm538","article-title":"Characterization of the G-quadruplexes in the duplex nuclease hypersensitive element of the PDGF-A promoter and modulation of PDGF-A promoter activity by TMPyP4","volume":"35","author":"Qin","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2021111619022395100_B18","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.canlet.2007.11.017","article-title":"Antitumor activity of G-quadruplex-interactive agent TMPyP4 in K562 leukemic cells","volume":"261","author":"Mikami-Terao","year":"2008","journal-title":"Cancer Lett."},{"key":"2021111619022395100_B19","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1053\/j.seminoncol.2006.04.012","article-title":"Drug targeting of the c-MYC promoter to repress gene expression via a G-quadruplex silencer element","volume":"33","author":"Hurley","year":"2006","journal-title":"Semin. Oncol."},{"key":"2021111619022395100_B20","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1002\/mc.22330","article-title":"An intramolecular G-quadruplex structure formed in the human MET promoter region and its biological relevance","volume":"55","author":"Yan","year":"2016","journal-title":"Mol. Carcinog."},{"key":"2021111619022395100_B21","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1089\/154545703322860825","article-title":"Analysis of thermal melting curves","volume":"13","author":"Mergny","year":"2003","journal-title":"Oligonucleotides"},{"key":"2021111619022395100_B22","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1021\/jm0610088","article-title":"Stabilization of G-quadruplex DNA and down-regulation of oncogene c-myc by quindoline derivatives","volume":"50","author":"Ou","year":"2007","journal-title":"J. Med. Chem."},{"key":"2021111619022395100_B23","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.biochi.2008.02.020","article-title":"Structures, folding patterns, and functions of intramolecular DNA G-quadruplexes found in eukaryotic promoter regions","volume":"90","author":"Qin","year":"2008","journal-title":"Biochimie"},{"key":"2021111619022395100_B24","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0969-2126(93)90015-9","article-title":"Solution structure of the human telomeric repeat d[AG3(T2AG3)3] G-tetraplex","volume":"1","author":"Wang","year":"1993","journal-title":"Structure"},{"key":"2021111619022395100_B25","doi-asserted-by":"crossref","first-page":"5584","DOI":"10.1016\/j.bmc.2006.04.033","article-title":"The new models of the human telomere d[AGGG(TTAGGG)3] in K+ solution","volume":"14","author":"Xu","year":"2006","journal-title":"Bioorg. Med. Chem."},{"key":"2021111619022395100_B26","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1093\/nar\/gkl348","article-title":"Human telomeric sequence forms a hybrid-type intramolecular G-quadruplex structure with mixed parallel\/antiparallel strands in potassium solution","volume":"34","author":"Ambrus","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"2021111619022395100_B27","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1021\/ja055636a","article-title":"An intramolecular G-quadruplex structure with mixed parallel\/antiparallel G-strands formed in the human BCL-2 promoter region in solution","volume":"128","author":"Dai","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"2021111619022395100_B28","doi-asserted-by":"crossref","first-page":"10799","DOI":"10.1021\/ja010008o","article-title":"Folding of the thrombin aptamer into a G-quadruplex with Sr(2+): stability, heat, and hydration","volume":"123","author":"Kankia","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"2021111619022395100_B29","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1093\/nar\/gkr849","article-title":"Yin Yang 1 contains G-quadruplex structures in its promoter and 5\u2032-UTR and its expression is modulated by G4 resolvase 1","volume":"40","author":"Huang","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2021111619022395100_B30","doi-asserted-by":"crossref","first-page":"3064","DOI":"10.1093\/nar\/gkm111","article-title":"Guanines are a quartet\u2019s best friend: impact of base substitutions on the kinetics and stability of tetramolecular quadruplexes","volume":"35","author":"Gros","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2021111619022395100_B31","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.bbrc.2010.10.065","article-title":"Selective recognition of oncogene promoter G-quadruplexes by Mg2+","volume":"402","author":"Yan","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021111619022395100_B32","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1093\/nar\/gkg211","article-title":"Structural transition from antiparallel to parallel G-quadruplex of d(G4T4G4) induced by Ca2+","volume":"31","author":"Miyoshi","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"2021111619022395100_B33","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1093\/abbs\/gmu077","article-title":"Structure variations of TBA G-quadruplex induced by 2\u2032-O-methyl nucleotide in K+ and Ca2+ environments","volume":"46","author":"Zhao","year":"2014","journal-title":"Acta Biochimica et Biophysica Sinica"},{"key":"2021111619022395100_B34","doi-asserted-by":"crossref","first-page":"4598","DOI":"10.1093\/nar\/gkn380","article-title":"Intramolecularly folded G-quadruplex and i-motif structures in the proximal promoter of the vascular endothelial growth factor gene","volume":"36","author":"Guo","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2021111619022395100_B35","doi-asserted-by":"crossref","first-page":"20958","DOI":"10.1074\/jbc.271.34.20958","article-title":"The development and use of a DNA polymerase arrest assay for the evaluation of parameters affecting intrastrand tetraplex formation","volume":"271","author":"Weitzmann","year":"1996","journal-title":"J. Biol. Chem."},{"key":"2021111619022395100_B36","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1093\/nar\/27.2.537","article-title":"A DNA polymerase stop assay for G-quadruplex-interactive compounds","volume":"27","author":"Han","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"2021111619022395100_B37","doi-asserted-by":"crossref","first-page":"7698","DOI":"10.1093\/nar\/gkm538","article-title":"Characterization of the G-quadruplexes in the duplex nuclease hypersensitive element of the PDGF-A promoter and modulation of PDGF-A promoter activity by TMPyP4","volume":"35","author":"Qin","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2021111619022395100_B38","doi-asserted-by":"crossref","first-page":"8902","DOI":"10.1021\/ja002179j","article-title":"Selective interactions of cationic porphyrins with G-quadruplex structures","volume":"123","author":"Han","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"2021111619022395100_B39","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1093\/nar\/gkq926","article-title":"Evidence of the formation of G-quadruplex structures in the promoter region of the human vascular endothelial growth factor gene","volume":"39","author":"Sun","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"2021111619022395100_B40","doi-asserted-by":"crossref","first-page":"10515","DOI":"10.1021\/jp810638n","article-title":"Differential biophysical behavior of human telomeric RNA and DNA quadruplex","volume":"113","author":"Arora","year":"2009","journal-title":"J. Phys. Chem. B"},{"key":"2021111619022395100_B41","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1021\/bi062244n","article-title":"Structural basis for binding of porphyrin to human telomeres","volume":"46","author":"Parkinson","year":"2007","journal-title":"Biochemistry"},{"key":"2021111619022395100_B42","doi-asserted-by":"crossref","first-page":"F82","DOI":"10.1152\/ajprenal.00200.2002","article-title":"Sp1 and Sp3 transcription factors synergistically regulate HGF receptor gene expression in kidney","volume":"284","author":"Zhang","year":"2003","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"2021111619022395100_B43","first-page":"1057","article-title":"Sp1 regulates expression of MET, and ribozyme-induced down-regulation of MET in fibrosarcoma-derived human cells reduces or eliminates their tumorigenicity","volume":"24","author":"Liang","year":"2004","journal-title":"Int. J. Oncol."}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20171128\/808192\/bsr-2017-1128.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20171128\/808192\/bsr-2017-1128.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T19:47:56Z","timestamp":1637092076000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/37\/6\/BSR20171128\/58093\/A-novel-G-quadruplex-motif-in-the-Human-MET"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,29]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,12,22]]}},"URL":"https:\/\/doi.org\/10.1042\/bsr20171128","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"value":"0144-8463","type":"print"},{"value":"1573-4935","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,29]]},"article-number":"BSR20171128"}}