Use of microRNA Let-7 to control the replication specificity of oncolytic adenovirus in hepatocellular carcinoma cells
| Autor: | Jiahe Yang, Huanzhang Hu, Changqing Su, Linfang Li, Qijun Qian, Meng-Chao Wu, Sai-Qun Lv, Xinyuan Liu, Xiaoning Wang, Jiang Li, Jin Huajun, Yao Huang, Chengliang Zhou |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Adenoviridae Infections Cancer Treatment Gene Expression lcsh:Medicine Virus Replication Immunoenzyme Techniques Mice Molecular Cell Biology Gastrointestinal Cancers Basic Cancer Research Gene expression Luciferases lcsh:Science Oncolytic Virotherapy Mice Inbred BALB C Multidisciplinary Reverse Transcriptase Polymerase Chain Reaction Liver Neoplasms Middle Aged Signaling in Selected Disciplines Liver Oncology Hepatocellular carcinoma Medicine Female Adenovirus E1A Proteins Research Article Signal Transduction Oncolytic adenovirus Carcinoma Hepatocellular Blotting Western Genetic Vectors Green Fluorescent Proteins Mice Nude Gastroenterology and Hepatology Biology Microbiology Adenoviridae Cell Line Tumor Virology Gastrointestinal Tumors microRNA medicine Animals Humans RNA Messenger Cell Proliferation Oncogenic Signaling Cell growth lcsh:R Cancers and Neoplasms Hepatocellular Carcinoma medicine.disease Xenograft Model Antitumor Assays Molecular biology digestive system diseases Oncolytic virus MicroRNAs Viral replication Viruses and Cancer Cell culture lcsh:Q |
| Zdroj: | PLoS ONE, Vol 6, Iss 7, p e21307 (2011) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Highly selective therapy for hepatocellular carcinoma (HCC) remains an unmet medical need. In present study, we found that the tumor suppressor microRNA, let-7 was significantly downregulated in a proportion of primary HCC tissues (12 of 33, 36.4%) and HCC cell lines. In line with this finding, we have engineered a chimeric Ad5/11 fiber oncolytic adenovirus, SG7011(let7T), by introducing eight copies of let-7 target sites (let7T) into the 3' untranslated region of E1A, a key gene associated with adenoviral replication. The results showed that the E1A expression (both RNA and protein levels) of the SG7011(let7T) was tightly regulated according to the endogenous expression level of the let-7. As contrasted with the wild-type adenovirus and the control virus, the replication of SG7011(let7T) was distinctly inhibited in normal liver cells lines (i.e. L-02 and WRL-68) expressing high level of let-7 (>300 folds), whereas was almost not impaired in HCC cells (i.e. Hep3B and PLC/PRF/5) with low level of let-7. Consequently, the cytotoxicity of SG7011(let7T) to normal liver cells was successfully decreased while was almost not attenuated in HCC cells in vitro. The antitumor ability of SG7011(let7T)in vivo was maintained in mice with Hep3B xenograft tumor, whereas was greatly decreased against the SMMC-7721 xenograft tumor expressing a high level of let-7 similar with L-02 when compared to the wild-type adenovirus. These results suggested that SG7011(let7T) may be a promising anticancer agent or vector to mediate the expression of therapeutic gene, broadly applicable in the treatment for HCC and other cancers where the let-7 gene is downregulated. |
| Databáze: | OpenAIRE |
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