gga-miR-375 plays a key role in tumorigenesis post subgroup J avian leukosis virus infection.
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 3'-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.
College of Animal Science, South China Agricultural University, Guangzhou, P R China; Key Laboratory of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, P R China.
Hongxin
H
Li
College of Animal Science, South China Agricultural University, Guangzhou, P R China.
Huiqing
H
Shang
State Key Laboratory of Livestock and Poultry Breeding, Guangzhou, P R China.
Dingming
D
Shu
United States Department of Agriculture (USDA), Agriculture Research Service, Avian Disease and Oncology Laboratory, East Lansing, Michigan, United States of America.
Huanmin
H
Zhang
College of Animal Science, South China Agricultural University, Guangzhou, P R China.
Jun
J
Ji
College of Animal Science, South China Agricultural University, Guangzhou, P R China; Key Laboratory of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, P R China.
Baoli
B
Sun
College of Animal Science, South China Agricultural University, Guangzhou, P R China; Key Laboratory of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, P R China.
Hongmei
H
Li
College of Animal Science, South China Agricultural University, Guangzhou, P R China; Key Laboratory of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, P R China.
Qingmei
Q
Xie
D020413:3' Untranslated Regions / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001353:Avian Leukosis / Q000235:genetics / Q000378:metabolism*; D001354:Avian Leukosis Virus / Q000235:genetics / Q000378:metabolism*; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism; D016466:CHO Cells; D002472:Cell Transformation, Viral; D002642:Chick Embryo; D002645:Chickens; D006224:Cricetinae; D003412:Cricetulus; D005347:Fibroblasts; D016147:Genes, Tumor Suppressor; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*
D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D030161:Avian Proteins; D035683:MicroRNAs; D015513:Oncogene Proteins; D012334:RNA, Neoplasm