gga‑microRNA‑375 negatively regulates the cell cycle and proliferation by targeting Yes‑associated protein 1 in DF‑1 cells

Abstract

MicroRNAs (miRNAs/miRs) serve a key role in regulating the cell cycle and inducing tumorigenesis. Subgroup J of the avian leukosis virus (ALV-J) belongs to the family Retroviridae, subfamily Orthoretrovirinae and genus Alpharetrovirus that causes tumors in susceptible chickens. gga-miR-375 is downregulated and Yes-associated protein 1 (YAP1) is upregulated in ALV-J-induced tumors in the livers of chickens, and it has been further identified that YAP1 is the direct target gene of gga-miR-375. In the present study, it was found that ALV-J infection promoted the cell cycle and proliferation in DF-1 cells. As the cell cycle and cell proliferation are closely associated with tumorigenesis, further experiments were performed to determine whether gga-miR-375 and YAP1 were involved in these cellular processes. It was demonstrated that gga-miR-375 significantly inhibited the cell cycle by inhibiting G 1 to S/G 2 stage transition and decreasing cell proliferation, while YAP1 significantly promoted the cell cycle and proliferation. Furthermore, these cellular processes in DF-1 cells were affected by gga-miR-375 through the targeting of YAP1. Collectively, the present results suggested that gga-miR-375, downregulated by ALV-J infection, negatively regulated the cell cycle and proliferation via the targeting of YAP1.

Small RNA deep sequencing revealed microRNAs’ involvement in modulating cellular senescence and immortalization state

“…However, those 31 miRNAs were not only identified in the ZS-1 samples, but also in the primary and the 21st passage CEF samples. Another study reported that gga-miR-375 was identified in the DF-1 cells ( Zhang et al., 2020b ), which was identified in the primary CEF and the ZS-1 samples ( Supplementary Table S4 ), but not in the 21st passage CEF samples. By comparing the 3 lists of identified miRNAs of the 3 types of cell samples, a total of 42 miRNAs (18 known and 24 novel miRNAs) was found present only on the list of the primary CEF samples; 5 novel miRNAs were identified only in the 21st passage CEF samples; and a set of different 5 novel miRNAs was detected only in the ZS-1 cells.…”

MicroRNAs: exploring their role in farm animal disease and mycotoxin challenges

“…Further, co-infection of reticuloendotheliosis virus (REV) and avian leukosis virus subgroup J (ALV-J) in vitro promotes viral replication by synergistically increasing exosomal miRNAs (miR-184-3p, miR-146a-3p, miR-146a-5p, miR-3538, and miR-155). Further, the downregulation of gga-miR-375 and the upregulation of YAP1 caused by ALV-J infection affect the cell cycle, leading to tumor formation ( 75 ). Together, these studies contribute to our understanding of the complex relationship between miRNAs and ALV infections and provide potential targets to control ALV-associated diseases in chickens.…”

Avian Leucosis Virus-Host Interaction: The Involvement of Host Factors in Viral Replication

“…Gga-miR-221 deregulates the G1/S transition by targeting cyclin-dependent kinase inhibitor 1B (CDKN1B), promoting cell proliferation and cell cycle progression ( 61 ). Gga-miR-375 and gga-miR-148A-5p could inhibit cell proliferation by targeting Yes-associated protein 1 (YAP1) and PDPK1, respectively ( 62 – 64 ). Several viruses were found to encode miRNAs, targeting cellular or viral mRNAs to promote an intracellular environment favorable to the completion of the viral life cycle ( 65 ).…”

“…Upon ALV-J infection, gga-miR-375 was significantly down-regulated, while circ-Vav3 was up-regulated. The circ-Vav3/gga-miR-375 and its target YAP1 induces epithelial-mesenchymal transition (EMT) through influencing EMT markers to promote tumorigenesis ( 62 , 63 ). The non-coding RNAs play multiple roles in ALV replication.…”