MicroRNA-33a-3p suppresses cell migration and invasion by directly targeting PBX3 in human hepatocellular carcinoma.
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.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China.|Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China.
Shu-Yan
SY
Han
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China.|Department of Biobank, Peking University Cancer Hospital & Institute, Beijing 100142, PR China.
Hai-Bo
HB
Han
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China.|Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, PR China.
Xiu-Yun
XY
Tian
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China.|Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China.
Hong
H
Sun
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China.|Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China.
Dong
D
Xue
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China.|Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China.
Can
C
Zhao
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China.|Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China.
Shan-Tong
ST
Jiang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China.|Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China.
Xi-Ran
XR
He
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China.|Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China.
Wen-Xian
WX
Zheng
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China.|Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China.
Jing
J
Wang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China.|Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China.
Li-Na
LN
Pang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China.|Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China.
Xiao-Hong
XH
Li
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China.|Department of Integrative Medicine and Geriatric Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China.
Ping-Ping
PP
Li
D020413:3' Untranslated Regions; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D056945:Hep G2 Cells; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011518:Proto-Oncogene Proteins / Q000378:metabolism*
D020413:3' Untranslated Regions; D018398:Homeodomain Proteins; C550416:MIRN33a microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C090466:proto-oncogene protein Pbx3
PBX3; hepatocellular cancer (HCC); metastasis; miR-33a-3p; migration