title: Bioinformatics analysis identifies miR-221 as a core regulator in hepatocellular carcinoma and its silencing suppresses tumor properties.
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.
authors.affiliation: Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Xing-Xing
authors.initials: XX
authors.lastname: He
authors.affiliation: 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.
authors.forename: An-Yuan
authors.initials: AY
authors.lastname: Guo
authors.affiliation: School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Chuan-Rui
authors.initials: CR
authors.lastname: Xu
authors.affiliation: Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chang
authors.affiliation: School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Guang-Ya
authors.initials: GY
authors.lastname: Xiang
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Gong
authors.affiliation: Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Zi-Li
authors.initials: ZL
authors.lastname: Dan
authors.affiliation: Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: De-An
authors.initials: DA
authors.lastname: Tian
authors.affiliation: Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Jia-Zhi
authors.initials: JZ
authors.lastname: Liao
authors.affiliation: Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Ju-Sheng
authors.initials: JS
authors.lastname: Lin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019295:Computational Biology / Q000379:methods*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D009368:Neoplasm Transplantation; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D051017:Apoptosis Regulatory Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C485792:ANGPTL2 protein, human; C438378:BBC3 protein, human; C486655:BMF protein, human; C525709:MIR221, human