start-ver=1.4 cd-journal=joma no-vol=131 cd-vols= no-issue=11 article-no= start-page=2537 end-page=2546 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=20121201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Runt-related transcription factor 3 reverses epithelial-mesenchymal transition in hepatocellular carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Loss or decreased expression of runt-related transcription factor 3 (RUNX3), a tumor suppressor gene involved in gastric and other cancers, has been frequently observed in hepatocellular carcinoma (HCC). The objective of this study was to identify the regulatory mechanism of the epithelialmesenchymal transition (EMT) by RUNX3 in HCC. Human HCC cell lines, Hep3B, Huh7, HLF and SK-Hep1, were divided into low- and high-EMT lines, based on their expression of TWIST1 and SNAI2, and were used in this in vitro study. Ectopic RUNX3 expression had an anti-EMT effect in low-EMT HCC cell lines characterized by increased E-cadherin expression and decreased N-cadherin and vimentin expression. RUNX3 expression has previously been reported to reduce jagged-1 (JAG1) expression; therefore, JAG1 ligand peptide was used to reinduce EMT in RUNX3-expressing low-EMT HCC cells. Immunohistochemical analyses were performed for RUNX3, E-cadherin, N-cadherin and TWIST1 in 33 human HCC tissues, also divided into low- and high-EMT HCC, based on TWIST1 expression. E-cadherin expression was correlated positively and N-cadherin expression was correlated negatively with RUNX3 expression in low-EMT HCC tissues. Correlations between EMT markers and RUNX3 mRNA expression were analyzed using Oncomine datasets. Similarly, mRNA expression of E-cadherin was also significantly correlated with that of RUNX3 in low-EMT HCC, while mRNA expression of JAG1 was negatively correlated with that of RUNX3. These results suggest a novel mechanism by which loss or decreased expression of RUNX3 induces EMT via induction of JAG1 expression in low-EMT HCC. en-copyright= kn-copyright= en-aut-name=TanakaShigetomi en-aut-sei=Tanaka en-aut-mei=Shigetomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShirahaHidenori en-aut-sei=Shiraha en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanishiYutaka en-aut-sei=Nakanishi en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishinaShin-Ichi en-aut-sei=Nishina en-aut-mei=Shin-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsubaraMinoru en-aut-sei=Matsubara en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakaokaNobuyuki en-aut-sei=Takaoka en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KataokaJunro en-aut-sei=Kataoka en-aut-mei=Junro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KuwakiKenji en-aut-sei=Kuwaki en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HagiharaHiroaki en-aut-sei=Hagihara en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ToshimoriJunichi en-aut-sei=Toshimori en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OhnishiHideki en-aut-sei=Ohnishi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TakakiAkinobu en-aut-sei=Takaki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakamuraShinichiro en-aut-sei=Nakamura en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NousoKazuhiro en-aut-sei=Nouso en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YagiTakahito en-aut-sei=Yagi en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YamamotoKazuhide en-aut-sei=Yamamoto en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=2 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=3 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=4 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=5 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=6 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=7 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=8 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=9 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=10 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=11 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=12 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=13 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=14 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=15 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=16 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=17 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol Surg Transplant & Surg Oncol affil-num=18 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol en-keyword=cell migration kn-keyword=cell migration en-keyword=tumor invasion kn-keyword=tumor invasion en-keyword=jagged-1 kn-keyword=jagged-1 en-keyword=E-cadherin kn-keyword=E-cadherin en-keyword=N-cadherin kn-keyword=N-cadherin END