Circular RNA and mRNA profiling reveal competing endogenous RNA networks during avian leukosis virus, subgroup J-induced tumorigenesis in chickens

Abstract

Avian leukosis virus subgroup J (ALV-J) can induce myeloid tumors and hemangiomas in chickens and causes severe economic losses with commercial layer chickens and meat-type chickens. Here, we generated ribominus RNA sequencing data from three normal chicken spleen tissues and three ALV-J-infected chicken spleen tissues. Structure analysis of transcripts showed that, compared to mRNAs and lncRNAs, chicken circRNAs shared relatively shorter transcripts and similar GC content. Differentially expression analysis showed 152 differentially expressed circRNAs with 106 circRNAs up regulated and 46 circRNAs down regulated. Through comparing differentially expressed circRNA host genes and mRNAs and performed ceRNA network analysis, we found several tumor or immune-related genes, in which, there were four genes existed in both differentially expressed mRNAs and circRNA host genes (Dock4, Fmr1, Zfhx3, Ralb) and two genes (Mll, Aoc3) involved in ceRNA network. We further characterized one exon-intron circRNA derived from HRH4 gene in the ceRNA network, termed circHRH4, which is an abundant and stable circRNA expressed in various tissues and cells in chicken and localizes in cytoplasm. Our results provide new insight into the pathology of ALV-J infection and circRNAs may also mediate tumorigenesis in chicken.

CircRNA Expression in Chicken Granulosa Cells Illuminated with Red Light

“…The identi ed DE circRNAs were widely distributed across most chromosomes, with the most on chr1 and the fewest on chr 32, in accordance with previous studies [23]. A total of 2,468 circRNAs were identi ed in GCs of SYFs, which is more than the number in liver of ALV-J-resistant chickens (1,800) [32] but less than the number in spleen of ALV-J-infected chickens (4,254) [33], possibly due to tissue-speci c factors. In total, 11,642 circRNAs of three types of GCs (SYF, F1, and F6) of chicken [23] and 4,204 circRNAs of two types of GCs (SYFs and large white follicles (LWFs)) were identi ed for duck follicles [22], both considerably more than identi ed herein, which indicates that the number of circRNAs may be closely correlated with the number of types of follicles.…”

Circular RNAs Are Regulators of Diverse Animal Transcriptomes: One Health Perspective

“…Future quantitative studies are speculated to reveal circRNAs are gene products of many animal viruses, which would raise the possibility for a novel diagnostic approach to detect these viruses. Significant primary sequence conservation has been discovered between circRNA of humans, old and new world monkeys, food animals, companion animals and murine species (Wang et al, 2014;Abdelmohsen et al, 2015;Chen et al, 2015;Ivanov et al, 2015;Venø et al, 2015;Zhang et al, 2016;Ouyang et al, 2018b;Qiu et al, 2018;Shangguan et al, 2018;Zhang F. et al, 2018). Sequence identity between circRNAs of mammals and flies indicate the fundamental steps in their biogenesis originated early in the evolution of life (Jeck et al, 2013;Memczak et al, 2013;Salzman et al, 2013).…”

“…Infection is the major concern to avoid in the production of high quality and quantity of poultry meat and eggs. Avian leukosis virus (ALV) infection heightens mortality of hens, reduces egg laying performance and diminishes the quality of eggs by reducing size and increasing fragility of the shell (Zhang et al, 2017;Qiu et al, 2018). The retrovirus infection is a major pathogen of both broilers and layer-type chickens and leads to enormous economic losses in the developing world and global poultry industry (Zhang et al, 2017).…”

“…Therefore, circRNA attenuation of mTOR activity by sequestering miRs was posited to be tumor-suppressive (Zhang et al, 2017). Qiu et al (2018) sequenced total RNA isolated from spleen of 20-weeks-old ALV-positive and ALV-negative chicken characterized as black-bone silky fowls. They reported the apparent loss of approximately 30% of circRNAs in ALV-infected chickens, aligning with the reported downregulation of circRNA in response to viral pathogens Liu C. X. et al, 2019).…”

Whole Transcriptome Analysis of Mesenchyme Tissue in Sika Deer Antler Revealed the CeRNAs Regulatory Network Associated With Antler Development

“…Currently, ceRNET is mainly used to solve human cancer treatment, among which the typical representative is the construction of PTEN's ceRNET. In addition, ceRNET has also been applied to explore biological characteristics in animal and plant research (Qiu et al, 2018;Bai et al, 2019;He et al, 2019;Li et al, 2019;Wang et al, 2019a). It is reasonable to hypothesized that ceRNET would be an exactly effective methods to reflect the complete and accurate regulate process of the antler rapidly development.…”