Design of miRNA sponges for MDV-1 as a therapeutic strategy against lymphomas.
Design of miRNA sponges for MDV-1 as a therapeutic strategy against lymphomas.
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DOI：
10.18632/oncotarget.23379
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发表时间：
2018-01-09
期刊：
影响因子：
--
通讯作者：
Cao Y
中科院分区：
文献类型：
--
作者：
Fang Y;Zhou Y;Zhang Y;He L;Xue C;Cao Y
淋巴瘤是含有淋巴样细胞的实体型肿瘤。在B和/或T淋巴细胞中建立的一些潜伏性疱疹病毒感染可导致淋巴瘤的形成。马立克氏病病毒血清型1（MDV-1）是一种引起鸟类淋巴组织增生性肿瘤的禽疱疹病毒，称为马立克氏病（MD）。MD常被用作研究病毒引起的淋巴瘤疾病发病机制的理想生物学模型。因此，我们以其为研究对象，研究miRNA海绵对其致瘤性的影响，为开发新的抗肿瘤小分子奠定理论基础。本研究设计的miRNA海绵能够特异性地结合并降解MDV-1 meq基因簇的miR-M2- 3 p、miR-M3- 5 p、miR-M5- 3 p、miR-M9- 5 p和miR-M12- 3 p。qPCR结果显示，miR-M9- 5 p和miR-M12- 3 p的敲除效率分别为85.03%、74.97%、47.06%、75.33%和62.55%。EDU染色和CCK-8结果显示，miRNA海绵在体外抑制MDV-1转化的MSB-1细胞增殖，miRNA海绵处理的细胞增殖率约为对照组的50%。DAPI染色和Annxin V-FITC/PI双染显示，miRNA海绵诱导MSB-1细胞凋亡，凋亡率较对照组增加约27.87%。transwell结果显示，miRNA海绵体在体外可抑制MSB-1细胞的侵袭，抑制率约为64.52%。软琼脂法显示，miRNA海绵对MSB-1细胞的体外致瘤能力有抑制作用，抑制率为66.44%; 60 d动物实验显示，miRNA海绵可减轻MSB-1细胞的生长抑制（约14.78%），降低死亡率（约16.00%）。此外，肿瘤形成率为0（对照组为8-12%），提示miRNA海绵可作为一种有效的抗肿瘤小分子，对疱疹病毒引起的肿瘤具有潜在的临床意义。
Lymphomas are solid-type tumors containing lymphoid cells. Some of latent herpesvirus infections established in B and/or T-lymphocytes could result in the formation of lymphomas. Marek's disease virus serotype 1 (MDV-1) is an avian herpes virus causing to lymphoproliferative tumors in birds, known as Marek’s disease (MD). MD has often been used as an ideal biological model for studying the pathogenesis of lymphoma diseases caused by viruses. Therefore, we used it as a research subject to study the effect of miRNA sponges on its tumorigenicity, and to develop the theoretical basis for a new anti-tumor small molecule. The miRNA sponges designed in this study specifically bind to and degrade the miRNAs of meq gene cluster of MDV-1, including miR-M2-3p, miR-M3-5p, miR-M5-3p, miR-M9-5p and miR-M12-3p.qPCR results showed that the knockdown efficiency was 85.03%, 74.97%, 47.06%, 75.33% and 62.55%, respectively. EDU staining and CCK-8 results showed that miRNA sponges inhibited the proliferation of MDV-1 transformed MSB-1 cells in vitro, and the proliferation rate of miRNA sponges-treated cells was about 50% of the control group. DAPI staining and Annxin V-FITC/PI double staining showed that miRNA sponges induced apoptosis in MSB-1 cells, and the apoptotic rate was increased by about 27.87% compared with the control group. The results of transwell showed that miRNA sponges could inhibit the invasion of MSB-1 cells in vitro, and the inhibitory rate was about 64.52%. The soft agar assay showed that miRNA sponges could inhibit the tumorigenic ability of MSB-1 cells in vitro, and the inhibitory rate was about 66.44%.The 60-days animal study showed that miRNA sponges could alleviate the growth inhibition of MSB-1 cells (about 14.78%) and reduce the mortality (about 16.00%). In addition, the tumor formation rate was 0 (8–12% in the control group).This study suggests that miRNA sponges can serve as an effective anti-tumor small molecule for the tumors caused by herpesvirus, with potential clinical implications.
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