Upregulated gga-miR-16-5p Inhibits the Proliferation Cycle and Promotes the Apoptosis of MG-Infected DF-1 Cells by Repressing PIK3R1-Mediated the PI3K/Akt/NF-κB Pathway to Exert Anti-Inflammatory Effect

Abstract

Mycoplasma gallisepticum (MG) mainly infects chickens to initiate chronic respiratory disease (CRD). microRNAs (miRNAs) play vital roles according to previously reported studies. Our previous study showed that gga-miR-16-5p, in MG-infected lungs of chicken embryo, was upregulated by Illumina sequencing. The study aimed to reveal what role gga-miR-16-5p plays in CRD progression. gga-miR-16-5p was upregulated in MG-infected fibroblast cells (DF-1). Phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) was demonstrated as the target gene of gga-miR-16-5p. Furthermore, PIK3R1 expression was lower in MG-infected groups than it in noninfected controls measured by qPCR. Additionally, overexpressed gga-miR-16-5p could downregulate PIK3R1 and phosphorylated serine/threonine kinase (p-Akt) to express protein, whereas there is an opposite effect on inhibition. Overexpressed gga-miR-16-5p resulted in decreased activity of tumor necrosis factor alpha (TNF-α) and the nuclear factor-kappaB (NF-κB) by qPCR. Furthermore, overexpressed gga-miR-16-5p restricted cell multiplication, cycle progression, and increased apoptosis of MG-infected DF-1 cells, whereas inhibited gga-miR-16-5p led to the opposite effect. Collectively, upregulated gga-miR-16-5p could decrease multiplication, cycle progression, and increase apoptosis of MG-infected DF-1 cells, at least partly through directly targeting PIK3R1 and inhibiting PI3K/Akt/NF-κB pathway to exert an anti-inflammatory effect. Our results will provide more experimental evidence to bring pathogenesis of MG infection to light.

Silencing of miR-17-5p suppresses cell proliferation and promotes cell apoptosis by directly targeting PIK3R1 in laryngeal squamous cell carcinoma

“…miR-486-5p, suppresses cell proliferation in non-small cell lung cancer by regulating PIK3R1 expression and modulating AKT pathway activation [40]. Furthermore, PIK3R1 level is reduced by miR-16-5p, which inhibits cell cycle and enhances cell apoptosis by modulating of the PI3K/AKT/NF-KB pathway [41]. Besides, miR-495, miR-106a-5p, miR-455 and miR-15 were directly or indirectly contribute to the regulation of PIK3R1 expression [42,43].…”

Overexpression of MicroRNA-16 Alleviates Atherosclerosis by Inhibition of Inflammatory Pathways

“…Upregulation of miR-16 by agomir significantly decreased the mRNA and protein levels of NF- κ B, NOD-like receptor protein 3 (NLRP3) inflammasome, and inflammatory factors in LPS-induced acute lung injury [ 26 ]. Furthermore, overexpressed miR-16-5p was revealed to restrict cell multiplication, cycle progression, and increased apoptosis of Mycoplasma gallisepticum- (MG-) infected fibroblast cells by decreasing the activity of TNF- α and NF- κ B [ 27 ]. Thus, miR-16 may be related with AS and CAD by participating in the inflammatory process.…”

Genome-wide analysis of differentially expressed profiles of mRNAs, lncRNAs and circRNAs in chickens during Eimeria necatrix infection

“…The downregulated PIK3R1 gene would be also regulated by TCONS_00018115. This gene was also downregulated during Mycoplasma gallisepticum (MG) infection, and it could be targeted by gga-miR-16-5p to inhibit cell proliferation and promote cell apoptosis through affecting the PI3K/Akt/NF-κB pathway, thereby exerting the antiinflammatory effect [109]. The downregulated SAM and SH3 domain-containing protein 1 (SASH1) would be trans-regulated by 24 lncRNAs (including 12 upregulated and 12 downregulated) and was associated with positive regulation of the p38 MAPK cascade.…”