title: HEY2, a target of miR-137, indicates poor outcomes and promotes cell proliferation and migration in hepatocellular carcinoma.
abstract: HEY2, a bHLH transcription factor, has been implicated in the progression of human cancers. Here, we showed that HEY2 expression was markedly increased in HCC, compared with the adjacent nontumorous tissues. High HEY2 expression was closely correlated with tumor multiplicity, tumor differentiation and TNM stage. Kaplan-Meier analyses revealed that HEY2 expression was significantly associated with poor overall and disease-free survival in a training cohort of 361 patients with HCC. The prognostic implication of HEY2 was validated in another cohort of 169 HCC patients. Multivariate Cox regression model indicated HEY2 as an independent factor for overall survival in HCC (Hazard ratio = 1.645, 95% confident interval: 1.309-2.067, P<0.001). We also demonstrated that HEY2 expression was inhibited by miR-137. In clinical samples, HEY2 expression was reversely associated to miR-137 expression. Furthermore, overexpression of HEY2 increased cell viabilities, colony formation and cell migration, whereas knockdown of HEY2 resulted in the opposite phenotypes. Collectively, our data suggest HEY2 as a promising biomarker for unfavorable outcomes and a novel therapeutic target for the clinical management of HCC.
authors.affiliation: Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Dan-Chun
authors.initials: DC
authors.lastname: Wu
authors.affiliation: Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Mei-Fang
authors.initials: MF
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The Affiliated Hexian Memorial Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Shu-Guang
authors.initials: SG
authors.lastname: Su
authors.affiliation: Department of Nursing, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Heng-Ying
authors.initials: HY
authors.lastname: Fang
authors.affiliation: Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xue-Hua
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Department of Pathology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Xie
authors.affiliation: Department of Emergency, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xu-Hui
authors.initials: XH
authors.lastname: Liu
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012097:Repressor Proteins; C405693:HEY2 protein, human; C545567:MIRN137 microRNA, human
keywords: HEY2; cell growth; hepatocellular carcinoma; miR-137; prognosis