Abstract
// Xinheng Zhang 1, 4, 5 , Yiming Yan 1, 4 , Xiaoya Lei 1, 4 , Aijun Li 2 , Huanmin Zhang 3 , Zhenkai Dai 1, 4 , Xinjian Li 1, 4 , Weiguo Chen 1, 4, 5 , Wencheng Lin 1, 4, 5 , Feng Chen 1, 4, 5 , Jingyun Ma 1, 4, 5 and Qingmei Xie 1, 4, 5 1 College of Animal Science, South China Agricultural University and Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Laboratory of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, 510642, P. R. China 2 College of Science and Engineering, Jinan University, Guangzhou, 510632, P. R. China 3 USDA, Agriculture Research Service, Avian Disease and Oncology Laboratory, East Lansing, MI, 48823, USA 4 Key Laboratory of Animal Health Aquaculture and Environmental Control, Guangdong, Guangzhou, 510642, P. R. China 5 South China Collaborative Innovation Center for Poultry Disease Control and Product Safety, Guangzhou, 510642, P. R. China Correspondence to: Qingmei Xie, email: qmx@scau.edu.cn Keywords: RNA sequencing; ALV-J; tumor; circular RNA; bioinformatics analysis Received: October 16, 2017 Accepted: December 05, 2017 Published: January 12, 2018 ABSTRACT ALV-J (subgroup J avian leucosis virus) is a kind of oncogenic exogenous retrovirus and diseases associated with ALV-J have caused severe reproduction problems in the poultry industry worldwide. However, the pathogenesis of ALV-J-induced tumor formation is still unclear. In recent years, circRNAs are validated to be related to cancer, which prompts us to explore whether aberrant expression of circRNAs exists in ALV-J-infected tumor samples. In this study, a total of 2822 differentially expressed circRNAs were detected by RNA sequencing in the tumor livers of ALV-J-susceptible chickens ( n = 3) and the normal liver samples of ALV-J-resistant chickens ( n = 3), among which 2808 circRNAs in the tumor liver samples were detected as unregulated compared to those in the normal liver samples. As circRNAs are considered as miRNA sponge, we predicted top 5 miRNA targets for 24 selected upregulated circRNAs in the ALV-J-induced tumor livers. CircRNA-miRNA-mRNA regulatory axes were also constructed to provide clear interaction relationship among them. Furthermore, Gene Ontology and KEGG pathway analyses were performed for miRNA target genes, the result of which implied that metabolism plays a key role in circRNAs alterations in ALV-J-induced tumor livers. In summary, we identified that circRNAs are involved in ALV-J-induced tumor formation in chickens. However, the pathogenicity mechanism still needs to be further explored.
Highlights
Circular RNA is a novel kind of endogenous noncoding RNA that form circular structures without 5′-3′ polarities and polyadenylated tails [1]
Our previous study showed that circular RNA (circRNA) alterations are involved in resistance to avian leucosis virus subgroup-J-induced tumor formation in chickens [17], no reports showed that circRNAs play a key role in chicken cancer which was induced by avian leucosis virus subgroup-J (ALV-J)
CircRNAs were sequenced in three tumor liver samples of ALV-J-susceptible chickens and three normal liver samples of ALV-J-resistance chickens
Summary
Circular RNA (circRNA) is a novel kind of endogenous noncoding RNA that form circular structures without 5′-3′ polarities and polyadenylated tails [1]. In 2017, two reports identified that circRNAs had the translation function [2, 3]. CircRNAs are enriched, conserved and stable in mammalian cells [7, 8]. It was reported that circRNAs function as microRNA (miRNA) sponges that naturally sequester and competitively suppress miRNA activity [9]. It was demonstrated that circRNAs are involved in the development of several types of diseases, such as atherosclerosis, myocardial Infarction and neuron injury [10,11,12]. There has been a special outpouring of concern for immense amounts www.impactjournals.com/oncotarget of research shown that circRNAs are associated with many human cancers, such as hepatocellular carcinoma [13], esophageal squamous cell carcinoma [14], human gastric cancer [15], colorectal cancer [16]. Our previous study showed that circRNA alterations are involved in resistance to avian leucosis virus subgroup-J-induced tumor formation in chickens [17], no reports showed that circRNAs play a key role in chicken cancer which was induced by avian leucosis virus subgroup-J (ALV-J)
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