Circular RNA Vav3 sponges gga-miR-375 to promote epithelial-mesenchymal transition
Circular RNA Vav3 sponges gga-miR-375 to promote epithelial-mesenchymal transition
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环状RNA Vav3海绵gga-miR-375促进上皮间质转化
DOI：
10.1080/15476286.2018.1564462
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发表时间：
2019-01
期刊：
影响因子：
4.1
通讯作者：
Xie Qingmei
中科院分区：
文献类型：
--
作者：
Zhang Xinheng;Yan Yiming;Lin Wencheng;Li Aijun;Zhang Huanmin;Lei Xiaoya;Dai Zhenkai;Li Xinjian;Li Hongxin;Chen Weiguo;Chen Feng;Ma Jingyun;Xie Qingmei
摘要环状RNA（circRNA）在进化上是保守的，广泛存在，但其功能仍不清楚。最近的发展强调了circRNA作为癌症中microRNA（miRNA）海绵的重要性。我们先前报道了通过microRNA微阵列分析，gga-miR-375在感染J亚群禽白血病病毒（ALV-J）的鸡的肝肿瘤中下调。根据先前的研究，可以合理地假设gga-miR-375可能与circRNA相关。然而，关于哪种circRNA充当gga-miR-375的海绵的问题仍有待回答。在本研究中，circRNA测序结果显示，在感染ALV-J的鸡的肝肿瘤中，被称为circ-Vav 3的circRNA Vav 3被上调。此外，RNA免疫沉淀（RIP）、生物素化RNA下拉和RNA荧光原位杂交（RNA-FISH）实验被进行以证实circ-Vav 3作为gga-miR-375的海绵。此外，我们通过双荧光素酶报告基因测定证实YAP 1是gga-miR-375的靶基因。我们的结论进一步验证了circ-Vav 3的海绵功能对其下游基因的影响，即circ-Vav 3的海绵功能可以消除gga-miR-375靶基因YAP 1，并增加YAP 1的表达水平。我们进一步证实了circ-Vav 3/gga-miR-375/YAP 1轴通过影响EMT标志物促进肿瘤发生而诱导上皮-间质转化（EMT）。最后，收集临床ALV-J诱导的肿瘤肝脏，检测核心基因的表达水平，为所得出的致瘤机制提供证据。总之，我们的结果表明，circ-Vav 3/gga-miR-375/YAP 1轴是肿瘤发生的另一个调节因子。
ABSTRACT Circular RNAs (circRNAs) are evolutionarily conserved and widely present, but their functions remain largely unknown. Recent development has highlighted the importance of circRNAs as the sponge of microRNA (miRNA) in cancer. We previously reported that gga-miR-375 was downregulated in the liver tumors of chickens infected with avian leukosis virus subgroup J (ALV-J) by microRNA microarray assay. It can be reasonably assumed in accordance with previous studies that the gga-miR-375 may be related to circRNAs. However, the question as to which circRNA acts as the sponge for gga-miR-375 remains to be answered. In this study, circRNA sequencing results revealed that a circRNA Vav3 termed circ-Vav3 was upregulated in the liver tumors of chickens infected with ALV-J. In addition, RNA immunoprecipitation (RIP), biotinylated RNA pull-down and RNA-fluorescence in situ hybridization (RNA-FISH) experiments were conducted to confirm that circ-Vav3 serves as the sponge of gga-miR-375. Furthermore, we confirmed through dual luciferase reporter assay that YAP1 is the target gene of gga-miR-375. The effect of the sponge function of circ-Vav3 on its downstream genes has been further verified by our conclusion that the sponge function of circ-Vav3 can abrogate gga-miR-375 target gene YAP1 and increase the expression level of YAP1. We further confirmed that the circ-Vav3/gga-miR-375/YAP1 axis induces epithelial-mesenchymal transition (EMT) through influencing EMT markers to promote tumorigenesis. Finally, clinical ALV-J-induced tumor livers were collected to detect core gene expression levels to provide a proof to the concluded tumorigenic mechanism. Together, our results suggest that circ-Vav3/gga-miR-375/YAP1 axis is another regulator of tumorigenesis.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
DOI：
--
发表时间：
1997
期刊：
--
影响因子：
--
作者：
L. N. Payne
通讯作者：
L. N. Payne
DOI：
10.1016/j.urolonc.2015.06.003
发表时间：
2015-10-01
影响因子：
2.7
作者：
Li, Shi;Yu, Zhe;Tan, Wan-Long
通讯作者：
Tan, Wan-Long
影响因子：
--
作者：
Li F;Zhang L;Li W;Deng J;Zheng J;An M;Lu J;Zhou Y
通讯作者：
Zhou Y
影响因子：
9.4
作者：
Gao, Yulong;Yun, Bingling;Wang, Xiaomei
通讯作者：
Wang, Xiaomei