HEY2, a target of miR-137, indicates poor outcomes and promotes cell proliferation and migration in hepatocellular carcinoma
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Dan-Chun Wu1,*, Mei-Fang Zhang2,*, Shu-Guang Su3,*, Heng-Ying Fang4, Xue-Hua Wang5, Dan He6, Yuan-Yuan Xie1, Xu-Hui Liu7
1Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
2Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China
3Department of Pathology, The Affiliated Hexian Memorial Hospital of Southern Medical University, Guangzhou, China
4Department of Nursing, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Pathology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
7Department of Emergency, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
*These authors have contributed equally to this work
Xu-Hui Liu, e-mail: [email protected]
Keywords: HEY2, miR-137, prognosis, cell growth, hepatocellular carcinoma
Received: December 21, 2015 Accepted: April 26, 2016 Published: May 13, 2016
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.
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