TTF-1 promoter operating miR-7 expression inhibits the growth of human lung cancer in vivo
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- 英文论文题名：TTF-1 promoter operating miR-7 expression inhibits the growth of human lung cancer in vivo
- 论文作者：Lei liangyu ; Chen chao ; Zhao Juanjuan ; Wang HaiRong ; Lin Xu
- 英文论文作者：Lei liangyu ; Chen chao ; Zhao Juanjuan ; Wang HaiRong ; Lin Xu ; Zunyi Medical College
- 年：2016
- 作者机构：Zunyi Medical College;
- 英文论文关键词：miR-7 ; TTF-1 ; 95D cells ; lung cancer ; growth
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R734.2
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：1
- 文件大小：1327k
- 原文格式：D
- 会议级别：全国
摘要
Recent evidence showed that microRNA-7(miR-7) was an important promising candidate for gene therapy of lung cancer. However, the therapeutic strategy on miR-7-based targeting expression in lung cancer remains to be elucidated. In the present study, we firstly constructed an eukaryotic expression vector of thyroid transcription factor(TTF-1) promoter operating expression of miR-7(termed as p-TTF-1-miR-7). we estimated the potential therapeutic effect of remote hypodermic injection, but not local injection, of p-TTF-1-miR-7 on human lung cancer cells in vivo using a nude mice model. We found that p-TTF-1-miR-7 was enriched in lung, liver and spleen, as well as tumor mass. Interestingly, the expression level of miR-7 remarkedly increased in tumor mass compared with that in other organs and tissues in vivo. Importantly, the growth and weight of tumors, as well as lung metastasis, also decreased significantly in remote hypodermic injection of p-TTF-1-miR-7 group, compared with those in control group. Further study showed that the proliferation of human lung cancer 95 D cells reduced obviously and cell apoptosis increased significantly, accompanied by reduced expression of phosph-Akt and phosph-Erk. Mechanism aspect, global gene expression analysis showed that the expression of NDUFA4, a novel putative target of miR-7, decreased significantly in tumor mass. Notably, we found that overexpression of NDUFA4 also could significantly abrogate the effect of p-TTF-1-miR-7 on the growth and migration of human lung cancer 95 D cells in vitro, accompanied altered transduction of Akt and Erk pathway.In all, our work indicated that TTF-1 promoter operating expression of miR-7 might be a novel useful and safety target therapeutic strategy against lung cancer, which provided novel insight into the implications for miRNA-based target expression therapy against clinical lung cancer.
Recent evidence showed that microRNA-7(miR-7) was an important promising candidate for gene therapy of lung cancer. However, the therapeutic strategy on miR-7-based targeting expression in lung cancer remains to be elucidated. In the present study, we firstly constructed an eukaryotic expression vector of thyroid transcription factor(TTF-1) promoter operating expression of miR-7(termed as p-TTF-1-miR-7). we estimated the potential therapeutic effect of remote hypodermic injection, but not local injection, of p-TTF-1-miR-7 on human lung cancer cells in vivo using a nude mice model. We found that p-TTF-1-miR-7 was enriched in lung, liver and spleen, as well as tumor mass. Interestingly, the expression level of miR-7 remarkedly increased in tumor mass compared with that in other organs and tissues in vivo. Importantly, the growth and weight of tumors, as well as lung metastasis, also decreased significantly in remote hypodermic injection of p-TTF-1-miR-7 group, compared with those in control group. Further study showed that the proliferation of human lung cancer 95 D cells reduced obviously and cell apoptosis increased significantly, accompanied by reduced expression of phosph-Akt and phosph-Erk. Mechanism aspect, global gene expression analysis showed that the expression of NDUFA4, a novel putative target of miR-7, decreased significantly in tumor mass. Notably, we found that overexpression of NDUFA4 also could significantly abrogate the effect of p-TTF-1-miR-7 on the growth and migration of human lung cancer 95 D cells in vitro, accompanied altered transduction of Akt and Erk pathway.In all, our work indicated that TTF-1 promoter operating expression of miR-7 might be a novel useful and safety target therapeutic strategy against lung cancer, which provided novel insight into the implications for miRNA-based target expression therapy against clinical lung cancer.
Recent evidence showed that microRNA-7(miR-7) was an important promising candidate for gene therapy of lung cancer. However, the therapeutic strategy on miR-7-based targeting expression in lung cancer remains to be elucidated. In the present study, we firstly constructed an eukaryotic expression vector of thyroid transcription factor(TTF-1) promoter operating expression of miR-7(termed as p-TTF-1-miR-7). we estimated the potential therapeutic effect of remote hypodermic injection, but not local injection, of p-TTF-1-miR-7 on human lung cancer cells in vivo using a nude mice model. We found that p-TTF-1-miR-7 was enriched in lung, liver and spleen, as well as tumor mass. Interestingly, the expression level of miR-7 remarkedly increased in tumor mass compared with that in other organs and tissues in vivo. Importantly, the growth and weight of tumors, as well as lung metastasis, also decreased significantly in remote hypodermic injection of p-TTF-1-miR-7 group, compared with those in control group. Further study showed that the proliferation of human lung cancer 95 D cells reduced obviously and cell apoptosis increased significantly, accompanied by reduced expression of phosph-Akt and phosph-Erk. Mechanism aspect, global gene expression analysis showed that the expression of NDUFA4, a novel putative target of miR-7, decreased significantly in tumor mass. Notably, we found that overexpression of NDUFA4 also could significantly abrogate the effect of p-TTF-1-miR-7 on the growth and migration of human lung cancer 95 D cells in vitro, accompanied altered transduction of Akt and Erk pathway.In all, our work indicated that TTF-1 promoter operating expression of miR-7 might be a novel useful and safety target therapeutic strategy against lung cancer, which provided novel insight into the implications for miRNA-based target expression therapy against clinical lung cancer.
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