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使用短发夹RNA表达载体抑制癌细胞中的端粒酶活性。

Inhibition of telomerase activity in cancer cells using short hairpin RNA expression vectors.

作者信息

Chen Shi-Ming, Tao Ze-Zhang, Hua Qing-Quan, Xiao Bo-Kui, Xu Yu, Wang Yan, Deng Yu-Qin

机构信息

Department of Otolaryngology-Head & Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.

出版信息

Cancer Invest. 2007 Dec;25(8):691-8. doi: 10.1080/07357900701561065.

Abstract

Telomerase activity is mainly regulated by the human telomerase reverse transcriptase (hTERT) gene. Our objective was to investigate the effect of short hairpin RNA (shRNA) directed against hTERT mRNA on telomerase activity in laryngeal cancer cells (Hep-2), nasopharyngeal carcinoma cells (NEC), and human bone marrow mesenchyme stem cells (hMSCs). Short hairpin RNA expression vectors targeting the messenger RNA of hTERT were constructed. Cells were treated with shRNA expression vectors directed against hTERT mRNA and control vectors that included mismatched shRNA. We found that treatment of special shRNA expression vectors induced significantly decrease in hTERT expression, telomerase activity, and cell viability in Hep-2 and NEC cells. In contrast, the shRNA control showed none of these effects. And none of these effects appeared in hMSCs cells. Our results suggest that shRNA against hTERT mRNA inhibits telomerase activity and cell viability through suppression of the hTERT expression in cancer cells. And this treatment has no side effect on healthy cells lack of telomerase activity. RNA interfering technology may be a promising strategy for the treatment of cancers.

摘要

端粒酶活性主要由人端粒酶逆转录酶(hTERT)基因调控。我们的目的是研究针对hTERT mRNA的短发夹RNA(shRNA)对喉癌细胞(Hep-2)、鼻咽癌细胞(NEC)和人骨髓间充质干细胞(hMSCs)中端粒酶活性的影响。构建了靶向hTERT信使RNA的短发夹RNA表达载体。用针对hTERT mRNA的shRNA表达载体和包括错配shRNA的对照载体处理细胞。我们发现,用特殊的shRNA表达载体处理可导致Hep-2和NEC细胞中hTERT表达、端粒酶活性和细胞活力显著降低。相比之下,shRNA对照未显示出这些效应。并且这些效应在hMSCs细胞中均未出现。我们的结果表明,针对hTERT mRNA的shRNA通过抑制癌细胞中的hTERT表达来抑制端粒酶活性和细胞活力。并且这种处理对缺乏端粒酶活性的健康细胞没有副作用。RNA干扰技术可能是一种有前景的癌症治疗策略。

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