CircRNA-5692 inhibits the progression of hepatocellular carcinoma by sponging miR-328-5p to enhance DAB2IP expression
Open Access
- 27 November 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 10 (12), 900
- https://doi.org/10.1038/s41419-019-2089-9
Abstract
Circular RNAs (circRNAs), one kind of noncoding RNAs, can interact with miRNA and transcription factors to regulate gene expression. However, little is known on which circRNA is crucial for the pathogenesis of hepatocellular carcinoma (HCC). CircRNA expression profile was analyzed by a microarray. Regulatory gene targets were predicted by bioinformatics analysis and validated by luciferase assay. Their expression was determined by qRT-PCR and Western blotting. DNA methylation was determined by methylation-specific PCR. Gene knockdown and overexpression were mediated by lentivirus-mediated shRNA and transfection with plasmids for cDNA expression, respectively. MTT assay, wound-healing assay, transwell invasion assay, and flow cytometry were used to determine malignant behaviors of HCC cells. HCC xenograft mouse model was used to determine the in vivo effects of circRNA-5692. CircRNA-5692 expression was downregulated in HCC tissues, and circRNA-5692 overexpression attenuated the malignant behaviors of HCC cells. Bioinformatics predicted that circRNA-5692 interacted with miR-328-5p, which targeted the DAB2IP mRNA. Actually, miR-328-5p promoted the malignant behaviors of HCC cells, while DAB2IP had opposite effects. Moreover, circRNA-5692 overexpression inhibited the growth of xenograft HCC tumors in vivo by decreasing miR-328-5p expression to enhance DAB2IP expression. In conclusion, the circRNA-5692–miR-328-5p–DAB2IP regulatory pathway inhibits the progression of HCC. Our findings may provide potential new targets for the diagnosis and therapy of HCC.Keywords
This publication has 45 references indexed in Scilit:
- EZH2-Regulated DAB2IP Is a Medulloblastoma Tumor Suppressor and a Positive Marker for SurvivalClinical Cancer Research, 2012
- miR-224 functions as an onco-miRNA in hepatocellular carcinoma cells by activating AKT signalingOncology Letters, 2012
- EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinomaEuropean Journal Of Cancer, 2012
- miR-221 Silencing Blocks Hepatocellular Carcinoma and Promotes SurvivalCancer Research, 2011
- Low expression of DAB2IP contributes to malignant development and poor prognosis in hepatocellular carcinomaJournal of Gastroenterology and Hepatology, 2011
- A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?Cell, 2011
- The Incidence and Epidemiology of Hepatocellular Carcinoma: A Global and Regional PerspectiveThe Oncologist, 2010
- An oncogene–tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-κBNature Medicine, 2010
- Vimentin induces changes in cell shape, motility, and adhesion during the epithelial to mesenchymal transitionThe FASEB Journal, 2010
- Differential expression of hDAB2IPA and hDAB2IPB in normal tissues and promoter methylation of hDAB2IPA in hepatocellular carcinomaJournal of Hepatology, 2007