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

He,Xing-Xing; Guo,An-Yuan; Xu,Chuan-Rui; Chang,Ying; Xiang,Guang-Ya; Gong,Jing; Dan,Zi-Li; Tian,De-An; Liao,Jia-Zhi; Lin,Ju-Sheng

doi:10.3892/or.2014.3306

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

Authors:
- Xing-Xing He
- An-Yuan Guo
- Chuan-Rui Xu
- Ying Chang
- Guang-Ya Xiang
- Jing Gong
- Zi-Li Dan
- De-An Tian
- Jia-Zhi Liao
- Ju-Sheng Lin
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Affiliations: Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, 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, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: July 3, 2014 https://doi.org/10.3892/or.2014.3306
Pages: 1200-1210

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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.

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