MicroRNA-33a-3p suppresses cell migration and invasion by directly targeting PBX3 in human hepatocellular carcinoma
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Shu-Yan Han1,2,*, Hai-Bo Han1,3,*, Xiu-Yun Tian1,4, Hong Sun1,2, Dong Xue1,2, Can Zhao1,2, Shan-Tong Jiang1,2, Xi-Ran He1,2, Wen-Xian Zheng1,2, Jing Wang1,2, Li-Na Pang1,2, Xiao-Hong Li1,2, Ping-Ping Li1,2
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China
2Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China
3Department of Biobank, Peking University Cancer Hospital & Institute, Beijing 100142, PR China
4Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, PR China
*These authors have contributed equally to this work
Shu-Yan Han, email: email@example.com
Ping-Ping Li, email: firstname.lastname@example.org
Keywords: hepatocellular cancer (HCC), migration, metastasis, miR-33a-3p, PBX3
Received: September 30, 2015 Accepted: May 23, 2016 Published: June 7, 2016
MicroRNAs (miRNAs) have been shown to function as either oncogenes or tumor suppressors by negatively regulating target genes involved in tumor initiation and progression. In this study, we demonstrated that down-regulation of miR-33a-3p in human primary hepatocellular cancer (HCC) specimens was significantly associated with metastases and poor survival. Over-expression of miR-33a-3p in HepG2 cells remarkably suppressed not only cell growth, migration and invasion, but also tumor growth and metastases in the chick embryo chorioallantoic membrane (CAM) assay, and down-regulated Pre-B-Cell Leukemia Homeobox 3 (PBX3) expression. Conversely, inhibition of miR-33a-3p in Bel-7402 cells resulted in increased of cell growth, spreading and invasion. Furthermore, rescue experiments by over-expression PBX3 completely eliminated the inhibitory effects of miR-33a-3p on tumor growth and metastasis, both in vitro and in vivo. The luciferase assay showed that 3’-untranslated regions (3’-UTRs) of PBX3 were inhibited significantly by miR-33a-3p, while mutations in the miR-33a-3p pairing residues rescued the luciferase expression. Taken together, our findings suggest that miR-33a-3p suppressed the malignant phenotype while also inhibiting PBX3 expression in hepatocellular cancer, implying that miR-33a-3p may be a promising biomarkers and therapy target for HCC intervention.
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