Episomal Lentiviral Vector-Mediated miR-145 Overexpression Inhibits Proliferation and Induces Apoptosis of Human Esophageal Carcinomas Cells

Author(s): Jun-He Zhang, Ai-Ling Du, Li Wang, Xiao-Yin Wang, Jian-Hui Gao, Tian-Yun Wang

Journal Name: Recent Patents on Anti-Cancer Drug Discovery

Volume 11 , Issue 4 , 2016

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Background: Gene therapy is a promising approach for the treatment of various cancers. However, most viral vectors used for this purpose carry risks, including potential integration into the host genome.

Objective: We addressed this issue in the present study by constructing an episomal lentiviral vector using the -interferon matrix attachment region to express the microRNA -145(miR-145), and examining the effect of miR-145 overexpression on human esophageal carcinomas (EC) cells. Some recent relevant patents are also discussed.

Method: Expression levels of miR-145 and the marker protein enhanced green fluorescent protein (EGFP) in infected ECA109 and EC9706 human esophageal carcinoma cells were detected by quantitative PCR and flow cytometry, respectively. Cell proliferation and apoptosis were assessed by Cell Counting Kit-8 and flow cytometry, respectively. Plasmid rescue experiments and fluorescence in situ hybridization were used to determine the episomal status of the transfected vector.

Results: We found that EGFP and miR-145 were highly expressed in EC cells, and miR-145 overexpression inhibited cell proliferation and induced apoptosis. Moreover, the lentiviral vector did not integrate into the host genome, but was maintained episomally at lower copy numbers.

Conclusion: Taken together, our results demonstrate that miR-145-expressing episomal lentiviral vectors are a promising tool for gene therapy in the treatment of EC.

Keywords: Apoptosis, episomal lentiviral vector, esophageal carcinoma, gene therapy, matrix attachment region, miR-145.

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Article Details

Year: 2016
Page: [453 - 460]
Pages: 8
DOI: 10.2174/1574892811666160822161157
Price: $65

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