A comprehensive analysis of avian lymphoid leukosis-like lymphoma transcriptomes including identification of LncRNAs and the expression profiles

Authors: DONG, KUNZHE - Augusta University; Heidari, Mohammad; Mays, Jody; CHANG, SHUANG - Shandong University; XIE, QINGMEI - South China Agricultural University; ZHANG, LEI - Chinese Academy Of Agricultural Sciences; AI, YONGXING - Jilin University; Zhang, Huanmin

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/29/2022
Publication Date: 8/8/2022
Citation: Dong, K., Heidari, M., Mays, J.K., Chang, S., Xie, Q., Zhang, L., Ai, Y., Zhang, H. 2022. A comprehensive analysis of avian lymphoid leukosis-like lymphoma transcriptomes including identification of LncRNAs and the expression profiles. PLOS ONE. 17(8):e0272557. https://doi.org/10.1371/journal.pone.0272557.
DOI: https://doi.org/10.1371/journal.pone.0272557

Interpretive Summary: It has been reported that some genetic lines of chickens spontaneously develop tumors without induction of tumor viruses or any known influence. This type of chicken lines was identified both in experimental and commercial farms. To understand the underlying causes of it, both normal control and such tumor samples were subjected to deep RNA sequence analyses and bioinformatics analyses. This study reports the findings of an epigenetic factor, known as long noncoding RNAs or LncRNAs, which are recently discovered RNA molecules that are longer than 200 nucleotides but do not code for any protein products. LncRNAs are reportedly to bind to DNA, RNA, protein to influence varied biological functions. This is the first-time report on epigenetic factor LncRNAs of the spontaneous tumors that differs from the normal control of the same line of chickens. This finding will help to understand the cause factors of this disease and to develop prevention strategies against this disease in chickens by breeding.

Technical Abstract: Avian lymphoid leukosis-like (LL-like) lymphoma has been observed in some experimental and commercial lines of chickens that are free of exogenous avian leukosis virus. Reported cases of avian lymphoid leukosis-like lymphoma incidences in the susceptible chickens are relatively low, but the apathogenic subgroup E avian leukosis virus (ALV-E) and the Marek’s disease vaccine, SB-1, significantly escalate the disease incidence in the susceptible chickens. However, the underlying mechanism of tumorigenesis is poorly understood. In this study, we bioinformatically analyzed the deep RNA sequences of 6 lymphoid leukosis-like lymphoma samples, collected from susceptible chickens post both ALV-E and SB-1 inoculation, and identified a total of 1,692 novel long non-coding RNAs (lncRNAs). Thirty-nine of those novel lncRNAs were detected with altered expression in the LL-like tumors. In addition, 13 lncRNAs whose neighboring genes also showed differentially expression and 2 conserved novel lncRNAs, XLOC_001407 and XLOC_022595, may have previously un-appreciated roles in tumor development in human. Furthermore, 14 lncRNAs, especially XLOC_004542, exhibited strong potential as competing endogenous RNAs via sponging miRNAs. The analysis also showed that ALV subgroup E viral gene Gag/Gag-pol and the MD vaccine SB-1 viral gene R-LORF1 and ORF413 were particularly detectable in the LL-like tumor samples. In addition, we discovered 982 novel lncRNAs that were absent in the current annotation of chicken genome and 39 of them were aberrantly expressed in the tumors. This is the first time that lncRNA signature is identified in avian lymphoid leukosis-like lymphoma and suggests the epigenetic factor, lncRNA, is involved with the avian lymphoid leukosis-like lymphoma formation and development in susceptible chickens. Further studies to elucidate the genetic and epigenetic mechanisms underlying the avian lymphoid leukosis-like lymphoma is indeed warranted.