PMID- 27285759 OWN - NLM STAT- MEDLINE DCOM- 20180122 LR - 20220311 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 7 IP - 27 DP - 2016 Jul 5 TI - MicroRNA-33a-3p suppresses cell migration and invasion by directly targeting PBX3 in human hepatocellular carcinoma. PG - 42461-42473 LID - 10.18632/oncotarget.9886 [doi] AB - 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. FAU - Han, Shu-Yan AU - Han SY AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China. AD - Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China. FAU - Han, Hai-Bo AU - Han HB AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China. AD - Department of Biobank, Peking University Cancer Hospital & Institute, Beijing 100142, PR China. FAU - Tian, Xiu-Yun AU - Tian XY AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China. AD - Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, PR China. FAU - Sun, Hong AU - Sun H AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China. AD - Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China. FAU - Xue, Dong AU - Xue D AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China. AD - Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China. FAU - Zhao, Can AU - Zhao C AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China. AD - Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China. FAU - Jiang, Shan-Tong AU - Jiang ST AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China. AD - Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China. FAU - He, Xi-Ran AU - He XR AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China. AD - Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China. FAU - Zheng, Wen-Xian AU - Zheng WX AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China. AD - Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China. FAU - Wang, Jing AU - Wang J AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China. AD - Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China. FAU - Pang, Li-Na AU - Pang LN AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China. AD - Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China. FAU - Li, Xiao-Hong AU - Li XH AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China. AD - Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China. FAU - Li, Ping-Ping AU - Li PP AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China. AD - Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China. LA - eng PT - Journal Article PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (3' Untranslated Regions) RN - 0 (Homeodomain Proteins) RN - 0 (MIRN33a microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Proto-Oncogene Proteins) RN - 146150-81-4 (proto-oncogene protein Pbx3) SB - IM MH - 3' Untranslated Regions MH - Carcinoma, Hepatocellular/genetics/*metabolism MH - Cell Movement MH - Cell Proliferation/genetics MH - Gene Expression Regulation, Neoplastic MH - HEK293 Cells MH - Hep G2 Cells MH - Homeodomain Proteins/*metabolism MH - Humans MH - Liver Neoplasms/genetics/*metabolism MH - MicroRNAs/*genetics MH - Neoplasm Invasiveness MH - Neoplasm Metastasis MH - Neoplasm Recurrence, Local MH - Proto-Oncogene Proteins/*metabolism PMC - PMC5173148 OTO - NOTNLM OT - PBX3 OT - hepatocellular cancer (HCC) OT - metastasis OT - miR-33a-3p OT - migration COIS- CONFLICTS OF INTERESTS The authors declare no potential conflicts of interest in the study. EDAT- 2016/06/11 06:00 MHDA- 2018/01/23 06:00 PMCR- 2016/07/05 CRDT- 2016/06/11 06:00 PHST- 2015/09/30 00:00 [received] PHST- 2016/05/23 00:00 [accepted] PHST- 2016/06/11 06:00 [pubmed] PHST- 2018/01/23 06:00 [medline] PHST- 2016/06/11 06:00 [entrez] PHST- 2016/07/05 00:00 [pmc-release] AID - 9886 [pii] AID - 10.18632/oncotarget.9886 [doi] PST - ppublish SO - Oncotarget. 2016 Jul 5;7(27):42461-42473. doi: 10.18632/oncotarget.9886.