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We investigated changes in expression of micro<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s (mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s) and the genes they regulate in tissues of patients with <jats:styled-content style=\"fixed-case\">HSCR<\/jats:styled-content>. Quantitative real\u2010time <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> and immunoblot analyses were used to measure levels of mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> mRNA<\/jats:styled-content>s, and proteins in colon tissues from 69 patients with <jats:styled-content style=\"fixed-case\">HSCR<\/jats:styled-content> and 49 individuals without <jats:styled-content style=\"fixed-case\">HSCR<\/jats:styled-content> (controls). Direct interactions between mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s and specific <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>s were indentified <jats:italic>in vitro<\/jats:italic>, while the function role of miR\u2010218\u20101 was investigated by using miR\u2010218 transgenic mice. An increased level of miR\u2010218\u20101 correlated with increased levels of <jats:styled-content style=\"fixed-case\">SLIT<\/jats:styled-content>2 and decreased levels of <jats:italic><jats:styled-content style=\"fixed-case\">RET<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">PLAG<\/jats:styled-content>1 <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein. The reductions in <jats:italic><jats:styled-content style=\"fixed-case\">RET<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">PLAG<\/jats:styled-content>1<\/jats:italic> by miR\u2010218\u20101 reduced proliferation and migration of <jats:styled-content style=\"fixed-case\">SH<\/jats:styled-content>\u2010SY5Y cells. Overexpression of the secreted form of <jats:italic><jats:styled-content style=\"fixed-case\">SLIT<\/jats:styled-content>2<\/jats:italic> inhibited cell migration <jats:italic>via<\/jats:italic> binding to its receptor <jats:italic><jats:styled-content style=\"fixed-case\">ROBO<\/jats:styled-content>1<\/jats:italic>. Bowel tissues from miR\u2010218\u20101 transgenic mice had nerve fibre hyperplasia and reduced numbers of gangliocytes, compared with wild\u2010type mice. Altered <jats:italic>miR\u2010218\u20101<\/jats:italic> regulation of <jats:italic>SLIT2, RET and PLAG1<\/jats:italic> might be involved in the pathogenesis of <jats:styled-content style=\"fixed-case\">HSCR<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/jcmm.12454","type":"journal-article","created":{"date-parts":[[2015,3,19]],"date-time":"2015-03-19T06:02:01Z","timestamp":1426744921000},"page":"1197-1207","source":"Crossref","is-referenced-by-count":41,"title":["<scp>SLIT<\/scp>2\/<scp>ROBO<\/scp>1\u2010miR\u2010218\u20101\u2010<scp>RET<\/scp>\/<scp>PLAG<\/scp>1: a new disease pathway involved in <scp>H<\/scp>irschsprung's disease"],"prefix":"10.1111","volume":"19","author":[{"given":"Weibing","family":"Tang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine Institute of Toxicology School of Public Health Nanjing Medical University Nanjing China"},{"name":"Laboratory of Modern Toxicology (Nanjing Medical University) Ministry of Education 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