Location: Avian Disease and Oncology ResearchTitle: gga-miR-375 plays a key role in tumorigenesis post subgroup J Avian Leukosis Virus infection) Author
Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/4/2014
Publication Date: 4/2/2014
Publication URL: http://handle.nal.usda.gov/10113/58666
Citation: Li, H., Shang, H., Shu, D., Zhang, H., Ji, J., Sun, B., Li, H., Xie, Q. 2014. gga-miR-375 plays a key role in tumorigenesis post subgroup J Avian Leukosis Virus infection. PLoS One. 9(4):e90878. Available: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0090878. Interpretive Summary: MicroRNAs or miRNAs are a class of small, non-coding RNAs that may be involved in many biological processes such as development, cell signaling, and immune response. Profiling and function analyses of miRNAs recently became an area of active research in all species. This study was designed to evaluate the function of a particular miRNA in chicken post the avian leukosis subgroup J virus infection, which is known as gga-miR-375. Our data indicated gga-miR-375 may act as a tumor suppressor partially controlling cancer cell proliferation and tumorigenesis. The finding would advance our understanding in genomic mechanism underlying disease resistance in poultry.
Technical Abstract: Avian leukosis is a neoplastic disease caused in part by subgroup J avian leukosis virus J (ALV-J). Micro ribonucleic acids (miRNAs) play pivotal oncogenic and tumour-suppressor roles in tumour development and progression. However, little is known about the potential role of miRNAs in avian leukosis tumours. We have found a novel tumour-suppressor miRNA, gga-miR-375, associated with avian leukosis tumorigenesis by miRNA microarray in a previous report. We have also previously studied the biological function of gga-miR-375; Overexpression of gga-miR-375 significantly inhibited DF-1 cell proliferation, and significantly reduced the expression of yes-associated protein 1 (YAP1) by repressing the activity of a luciferase reporter carrying the 39-untranslated region of YAP1. This indicates that gga-miR-375 is frequently downregulated in avian leukosis by inhibiting cell proliferation through YAP1 oncogene targeting. Overexpression of gga-miR-375 markedly promoted serum starvation induced apoptosis, and there may be the reason why the tumour cycle is so long in the infected chickens. In vivo assays, gga-miR-375 was significantly downregulated in chicken livers 20 days after infection with ALV-J, and YAP1 was significantly upregulated 20 days after ALV-J infection (P,0.05). We also found that expression of cyclin E, an important regulator of cell cycle progression, was significantly upregulated (P,0.05). Drosophila inhibitor of apoptosis protein 1 (DIAP1), which is related to caspase-dependent apoptosis, was also significantly upregulated after infection. Our data suggests that gga-miR-375 may function as a tumour suppressor thereby regulating cancer cell proliferation and it plays a key role in avian leukosis tumorigenesis.