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Oncol Rep. 2014 Sep;32(3):1200-10. doi: 10.3892/or.2014.3306. Epub 2014 Jul 3.

Bioinformatics analysis identifies miR-221 as a core regulator in hepatocellular carcinoma and its silencing suppresses tumor properties.

Author information

1
Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
2
Hubei Bioinformatics and Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P.R. China.
3
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

Abstract

Hepatocellular carcinoma (HCC) is a worldwide malignancy; however, there is a lack of effective targeted therapies. We and others have found that miR-221 is one of the most consistently overexpressed miRNAs in liver cancer. However, the roles of miR-221 in hepatocellular carcinogenesis are still not fully elucidated. In the present study, we used bioinformatics tools, gain- and loss-of-function methods to determine the roles of miR-221 in HCC. Bioinformatics analysis showed that miR-221 is a core miRNA which targets a large number of HCC-related genes and has formed many feed-forward regulatory loops combining transcription factors (TFs) to regulate HCC-related genes. Inhibition of miR-221 in liver cancer cells decreased cell proliferation, clonogenicity, migration/invasion and also induced G1 arrest and apoptosis. In addition, we demonstrated that miR-221 bound directly to the 3'-untranslated region of BMF, BBC3 and ANGPTL2, and inhibited the expression of BMF, BBC3 and ANGPTL2. In a mouse model, lentivirus‑mediated miR-221 silencing could significantly suppress the growth of hepatoma xenografts in nude mice. In conclusion, we showed that miR-221 is a critical modulator in the HCC signaling pathway, and miR-221 silencing inhibits liver cancer malignant properties in vitro and in vivo, which may benefit the treatment for patients with unresectable HCC.

PMID:
24993451
DOI:
10.3892/or.2014.3306
[Indexed for MEDLINE]

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