Role of gga-miR-29b-3p in suppressing the proliferation, invasion and migration of MSB1 Marek's disease tumor cells by the targeting of the DNMT3B gene.
Role of gga-miR-29b-3p in suppressing the proliferation, invasion and migration of MSB1 Marek's disease tumor cells by the targeting of the DNMT3B gene.
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DOI：
10.21037/atm-22-3519
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发表时间：
2022-08
影响因子：
--
通讯作者：
Jin, Erhui
中科院分区：
文献类型：
--
作者：
Han, Yujiao;Lian, Ling;Ren, Man;Li, Shenghe;Zhao, Chunfang;Jin, Erhui
马立克氏病 (MD) 是一种主要影响家禽的 II 类传染性淋巴组织增生性疾病，已被证明会导致消瘦、肢体瘫痪，并常常导致急性死亡。它是由细胞结合疱疹病毒引起的肿瘤性疾病，导致各种器官和组织形成肿瘤。我们之前的报告发现microRNA gga-miR-29b-3p在MD淋巴瘤中表现出异常表达。然而，gga-miR-29b-3p是否影响MD肿瘤发生仍不清楚。选择MD肿瘤细胞系MSB1来分析肿瘤中gga-miR-29b-3p的特征。分别通过细胞计数试剂盒（CCK-8）和Transwell评估细胞增殖和迁移，并分别通过荧光染色和流式细胞术分析细胞凋亡和周期。通过双荧光素酶结果和功能丧失测定验证了 gga-miR-29b-3p 及其潜在靶基因之间的调节。通过检查MSB1细胞的RNA干扰程度来验证靶基因的效果。分析显示，gga-miR-29b-3p 损害 MSB1 MD 肿瘤细胞系的增殖，诱导细胞凋亡，但对细胞周期没有明显影响，并抑制侵袭相关的 MMP2 和 MMP9 基因的表达。结论是DNMT3B是gga-miR-29b-3p的直接靶标。正如预期的那样，使用小干扰 RNA (siRNA) 敲低 DNMT3B 对 MSB1 细胞增殖、凋亡和周期的影响与 gga-miR-29b-3p 过表达相关。此外，在 gga-miR-29b-3p 过表达组和 DNMT3B 敲低组中，BCL2 和 BCL2L1 下调，TNFSF10 上调。 DNMT3B 敲除后，侵袭相关基因的表达水平降低。在 gga-miR-29b-3p 过表达和 DNMT3B 敲低条件下，观察到 MD 病毒中 MEQ 癌基因表达的减少。总体而言，gga-miR-29b-3p 被证明通过靶向 DNMT3B 基因对 MD 淋巴瘤进展具有抑制作用。 Gga-miR-29b-3p过表达和DNMT3B敲低通过抑制凋亡途径中促凋亡基因表达并提高抗凋亡基因表达来抑制MSB1细胞增殖。我们的研究为MD的靶向治疗提供了理论依据。
Marek’s disease (MD), a class II infectious, lymphoproliferative disease that mainly afflicts poultry, has been shown to cause wasting, limb paralysis, and often acute death. It is a neoplastic disease caused by a cell-binding herpesvirus that leads to the formation of tumors in various organs and tissues. Our previous reports have found that the microRNA, gga-miR-29b-3p, showed abnormal expression in MD lymphoma. However, it remains unknown whether gga-miR-29b-3p affects MD tumorigenesis. The MD tumor cell line MSB1 was chosen to analyze the characteristics of gga-miR-29b-3p in tumors. Cell proliferation and migration were assessed by Cell Counting Kit-8 (CCK-8) and Transwell, respectively, and cell apoptosis and cycle were analyzed via fluorescent staining and flow cytometry, respectively. The regulation between gga-miR-29b-3p and its potential target genes was verified by dual luciferase results and loss-of-function assays. The effect of target genes was verified by examining the degree of RNA interference on MSB1 cells. Analysis revealed that gga-miR-29b-3p impaired the proliferation of the MSB1 MD tumor cell line, induced apoptosis without obvious effects on the cell cycle, and suppressed the expression of the invasion-associated MMP2 and MMP9 genes. It was concluded that DNMT3B is the direct target of gga-miR-29b-3p. As expected, the effects of DNMT3B knockdown with small interfering RNA (siRNA) on MSB1 cell proliferation, apoptosis, and cycle were associated with gga-miR-29b-3p overexpression. Moreover, BCL2 and BCL2L1 were downregulated and TNFSF10 was upregulated in both the gga-miR-29b-3p overexpression and DNMT3B knockdown groups. The expression levels of invasion-related genes were decreased post-DNMT3B knockdown. In both the gga-miR-29b-3p overexpression and DNMT3B knockdown conditions, a decrease in MEQ oncogene expression in MD virus was observed. Overall, gga-miR-29b-3p was demonstrated to have a suppressive effect in MD lymphoma progression via the targeting of the DNMT3B gene. Gga-miR-29b-3p overexpression and DNMT3B knockdown inhibited MSB1 cell proliferation through suppressing the pro-apoptotic gene expression and elevating the anti-apoptotic gene expression in the apoptosis pathway. Our study provides a theoretical basis for targeted treatment of MD.
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影响因子：
37.3
作者：
Andrews MC;Cursons J;Hurley DG;Anaka M;Cebon JS;Behren A;Crampin EJ
通讯作者：
Crampin EJ
影响因子：
4.3
作者：
Hill M;Tran N
通讯作者：
Tran N
gga-miR-155靶向RORA对马立克氏病病毒（MDV）转化细胞系MSB1细胞增殖、凋亡和侵袭的影响
影响因子：
2.6
作者：
Ding, Ke;Yu, Zu-Hua;Yu, Zu-Ling
通讯作者：
Yu, Zu-Ling
影响因子：
4.5
作者：
Bertzbach, Luca D.;van Haarlem, Daphne A.;Jansen, Christine A.
通讯作者：
Jansen, Christine A.
影响因子：
4.4
作者：
Li X;Chiang HI;Zhu J;Dowd SE;Zhou H
通讯作者：
Zhou H