An Artificially Designed Interfering lncRNA Expressed by Oncolytic Adenovirus Competitively Consumes OncomiRs to Exert Antitumor Efficacy in Hepatocellular Carcinoma

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-selecti...

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Bibliographic Details
Published in:Molecular cancer therapeutics 2016-07, Vol.15 (7), p.1436-1451
Main Authors: Li, Xiaoya, Su, Yinghan, Sun, Bin, Ji, Weidan, Peng, Zhangxiao, Xu, Yang, Wu, Mengchao, Su, Changqing
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Adenovirus
Animals
Apoptosis - genetics
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - pathology
Carcinoma, Hepatocellular - therapy
Cell Cycle - genetics
Cell Line, Tumor
Cell Movement - genetics
Cell Proliferation
Disease Models, Animal
Gene Expression
Gene Order
Genes, Reporter
Genetic Vectors - genetics
Humans
Liver Neoplasms - genetics
Liver Neoplasms - pathology
Liver Neoplasms - therapy
Male
Mice
MicroRNAs - genetics
Oncolytic Virotherapy
Oncolytic Viruses - genetics
RNA Interference
RNA, Long Noncoding - genetics
RNA, Messenger - genetics
Transcriptome
Tumor Burden - genetics
Virus Replication
Xenograft Model Antitumor Assays
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Summary: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.
ISSN:1535-7163
1538-8514
DOI:10.1158/1535-7163.MCT-16-0096