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Circular RNA Vav3 sponges gga-miR-375 to promote epithelial-mesenchymal transition

文献类型： 外文期刊

作者： Zhang, Xinheng 1 ; Yan, Yiming 1 ; Lin, Wencheng 1 ; Li, Aijun 6 ; Zhang, Huanmin 7 ; Lei, Xiaoya 1 ; Dai, Zhenkai 1 ; Li 1 ;

作者机构： 1.South China Agr Univ, Coll Anim Sci, Guangzhou 510642, Guangdong, Peoples R China

2.Minist Agr, Guangdong Prov Key Lab Agroanim Genom & Mol Breed, Guangzhou, Guangdong, Peoples R China

3.Minist Agr, Key Lab Chicken Genet Breeding & Reprod, Guangzhou, Guangdong, Peoples R China

4.Dept Sci & Technol Guangdong Prov, Key Lab Anim Hlth Aquaculture & Environm Control, Guangzhou, Guangdong, Peoples R China

5.South China Collaborat Innovat Ctr Poultry Dis Co, Dept Sci & Technol Guangdong Prov, Guangzhou, Guangdong, Peoples R China

6.Jinan Univ, Coll Sci & Engn, Guangzhou, Guangdong, Peoples R China

7.ARS, USDA, Avian Dis & Oncol Lab, E Lansing, MI USA

关键词： circ-Vav3; ALV-J; YAP1; gga-miR-375; EMT

期刊名称：RNA BIOLOGY （ 影响因子：4.652； 五年影响因子：6.774 ）

ISSN： 1547-6286

年卷期： 2019 年 16 卷 1 期

页码：

收录情况： SCI

摘要： 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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