title: An Artificially Designed Interfering lncRNA Expressed by Oncolytic Adenovirus Competitively Consumes OncomiRs to Exert Antitumor Efficacy in Hepatocellular Carcinoma.
abstract: Endogenous miRNAs, especially oncogenic miRNAs (OncomiR), have been molecular targets for cancer therapy. We generated an artificially designed interfering long noncoding RNA (lncRNAi), which contains the sequences that can complementarily bind to multiple OncomiRs and is expressed by cancer-selectively replicating adenovirus. The adenovirus-expressed lncRNAi with high levels in hepatocellular carcinoma (HCC) cells competes with OncomiR target genes to bind to and consume OncomiRs, thereby achieving the targeted anti-HCC efficacy. With the targeting replication of adenovirus in HCC cells, lncRNAi was highly expressed and resulted in decreased abilities of proliferation, migration, and invasion, induced cell-cycle changes and apoptosis, and markedly changed the cellular mRNA and miRNA expression profiles in HCC cells. The optimal antitumor effect was also demonstrated on HCC cell line xenograft models and HCC patient-derived xenograft (PDX) tumor models in nude mice. This strategy has established a technology platform with a reliable therapeutic effect for HCC therapy. Mol Cancer Ther; 15(7); 1436-51. ©2016 AACR.
authors.affiliation: Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center for Liver Cancer, Second Military Medical University, Shanghai, China.
authors.forename: Xiaoya
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Life Science, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Yinghan
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center for Liver Cancer, Second Military Medical University, Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center for Liver Cancer, Second Military Medical University, Shanghai, China.
authors.forename: Weidan
authors.initials: W
authors.lastname: Ji
authors.affiliation: Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center for Liver Cancer, Second Military Medical University, Shanghai, China.
authors.forename: Zhangxiao
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center for Liver Cancer, Second Military Medical University, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center for Liver Cancer, Second Military Medical University, Shanghai, China.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center for Liver Cancer, Second Military Medical University, Shanghai, China. Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical College, Xuzhou, China. suchangqing@gmail.com.
authors.forename: Changqing
authors.initials: C
authors.lastname: Su
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015870:Gene Expression; D023061:Gene Order; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D059467:Transcriptome; D047368:Tumor Burden / Q000235:genetics; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012333:RNA, Messenger