title: Role of microRNA-95 in the anticancer activity of Brucein D in hepatocellular carcinoma.
abstract: Brucea javanica fruit has been used to treat amebic dysentery, malaria and various parasites and it has been applied as an anti-cancer agent in Traditional Chinese Medicine. Brucein D (BD) is a naturally occurring compound extracted from Brucea javanica fruit which shows anti-cancer activity against pancreatic cancer. Here, we further demonstrated that BD inhibited hepatocellular carcinoma (HCC) cell growth in vitro and tumor growth in vivo that were attributed to the induction of cell apoptosis. BD did not exert growth inhibition on non-tumorigenic human hepatocytes. MTT assay was used to measure cell viability. Annexin V and TUNEL assay were applied to identify apoptotic cells in cell suspension and in tissue section respectively. Downstream micro-RNA (miRNA) targets of BD were screened out by miRNA array. miRNAs and their target proteins were identified by bioinformatics analysis and luciferase reporter assay. 39 miRNAs regulated by BD in HCC were identified. miR-95 was found to be a potential drug target of BD. We further identified CUG triplet repeat RNA-binding protein 2 (CUGBP2) as the downstream target of miR-95. Our data suggested that BD exerted its anti-cancer activity against HCC through modulation of miR-95 expression.
authors: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
authors: Zhangang
authors: Z
authors: Xiao
authors: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
authors: Sheung
authors: S
authors: Ching Chow
authors: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
authors: Chi
authors: C
authors: Han Li
authors: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
authors: Shing
authors: S
authors: Chun Tang
authors: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
authors: Stephen K W
authors: SK
authors: Tsui
authors: School of Chinese Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
authors: Zhixiu
authors: Z
authors: Lin
authors: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China. Electronic address: frankch@cuhk.edu.hk.
authors: Yangchao
authors: Y
authors: Chen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D032269:Brucea / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D005638:Fruit / Q000737:chemistry; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D036702:Quassins / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C575854:MIRN95 microRNA, human; D035683:MicroRNAs; D036702:Quassins; C030412:bruceine D
keywords: BD (PucChem CID: 122784); Brucein D; Hepatocellular carcinoma; MicroRNA-95