Regression of A549 lung cancer tumors by anti-miR-150 vector
Regression of A549 lung cancer tumors by anti-miR-150 vector
复制标题
通过抗 miR-150 载体消退 A549 肺癌肿瘤。
DOI：
10.3892/or.2011.1466
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发表时间：
2012-01-01
期刊：
影响因子：
4.2
通讯作者：
Xie, Shu-Yang
中科院分区：
文献类型：
--
作者：
Li, You-Jie;Zhang, Yan-Xa;Xie, Shu-Yang
microRNA（miRNAs）已被证明在癌症中发挥作用。反义寡核苷酸可以直接与miRNAs结合并阻断其活性，通常称为anti-miRNAs。为了通过抗miRNAs在体外和体内抑制A549细胞增殖，构建了受HI启动子调控的抗miR-150表达载体（PR-ASO-150），该载体含有在发夹之后终止转录的“TTTTT”序列。观察PR-ASO-150处理后A549细胞在体外或裸鼠中的增殖。结果显示，PR-ASO-150处理组miR-150表达受到抑制，且A549细胞的生长抑制率高于对照组，表明PR-ASO-150可通过调控miR-150的表达抑制A549细胞的增殖。在裸鼠中建立A549癌细胞异种移植物后，瘤内递送PR-ASO-150以研究通过调节miR-150表达对肿瘤增殖的抑制作用。结果表明，与对照组相比，肿瘤体积和重量较低。我们的结果进一步表明，用PR-ASO-150处理肿瘤组织后，p53表达更高，表明p53的上调有助于抑制肿瘤生长。我们的研究通过开发抗miRNAs为癌症治疗提供了一种新的策略。
microRNAs (miRNAs) have been shown to play a role in cancer. Antisense oligonucleotides can bind directly to miRNAs and block their activity, which are generally named anti-miRNAs. To suppress A549 cell proliferation in vitro and in vivo by anti-miRNAs, an anti-miR-150 expression vector (PR-ASO-150), regulated by the HI promoter and containing a 'TTTTT' sequence following a hairpin to stop transcription, was constructed. A549 cell proliferation in vitro or in nude mice was observed after PR-ASO-150 treatment. Our results showed that miR-150 expression was inhibited and the growth inhibition rate of A549 cells was higher in the PR-ASO-150-treated group compared with the control, which indicated that PR-ASO-150 could inhibit A549 cell proliferation by regulating miR-150 expression. Following establishment of A549 cancer cell xenografts in nude mice, PR-ASO-150 was delivered intratumorally to investigate the suppressive action to tumor proliferation by regulating miR-150 expression. The results indicate that the tumor volume and weight were lower compared to the control group. Our results further showed that p53 expression was higher after tumor tissue was treated with PR-ASO-150, indicating that up-regulation of p53 contributed to the suppression to tumor growth. Our study provides a novel strategy for cancer therapy through the development of anti-miRNAs.