CircRNA-5692 inhibits the progression of hepatocellular carcinoma by sponging miR-328-5p to enhance DAB2IP expression

被引:207
作者
Liu, Zhenguo [1 ,2 ]
Yu, Yaqun [3 ]
Huang, Zebing [1 ]
Kong, Yi [4 ]
Hu, Xingwang [1 ]
Xiao, Wei [2 ]
Quan, Jun [1 ]
Fan, Xuegong [1 ]
机构
[1] Cent South Univ, Xiangya Hosp, Dept Infect Dis, Hunan Key Lab Viral Hepatitis, Changsha 410008, Hunan, Peoples R China
[2] Cent South Univ, Xiangya Hosp 3, Dept Infect Dis, Changsha 410013, Hunan, Peoples R China
[3] Guilin Med Coll, Affiliated Hosp, Dept Hepatobiliary & Pancreat Surg, Guilin 541002, Peoples R China
[4] Hunan Canc Hosp, Dept Hepatopancreatobiliary Med, Changsha 410013, Hunan, Peoples R China
关键词
CIRCULAR RNA; MECHANISMS; MARKER;
D O I
10.1038/s41419-019-2089-9
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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页数:14
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