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Stress-induced immunosuppression (SIIS) is one of the common problems in intensive poultry production, which often reduces the prevention and control effects of various vaccines, including infectious bursal disease virus (IBDV) vaccine, and brings enormous economic losses to the poultry industry. However, the molecular mechanisms of SIIS inhibiting immune response to IBDV vaccine remain unclear. In this study, suppressor of cytokine signaling 3 ( SOCS3 ) gene was selected and stress-induced immunosuppressed chickens were simulated using dexamethasone (Dex). Quantitative real-time PCR (qRT-PCR) was conducted to analyze its expression characteristics and game relationships between SOCS3 gene and miR-27b-3p (it could target SOCS3 gene) in the process of SIIS inhibiting immune response to IBDV vaccine in chicken, and the potential application value of circulating miR-27b-3p as a biomarker was also identified. The results showed that SOCS3 gene and miR-27b-3p were significantly differentially expressed in the candidate tissues during SIIS inhibiting the immune response to IBDV (P < 0.05), respectively, which were key factors involved in the process. Moreover, miR-27b-3p and SOCS3 gene showed game regulation relationships in several tissues during the process, so the miR-27b-3p/SOCS3 regulatory network was one of the key mechanisms of SOCS3 gene participating in the process. Circulating miR-27b-3p was differentially expressed in serum at 10 time points (1, 2, 3, 4, 5, 7, 14, 21, 28, and 35 days postimmunization (dpi)) in the process (P < 0.05), showing that circulating miR-27b-3p was a valid candidate target as a molecular marker for detecting SIIS inhibiting the IBDV immune response. This study can provide references for further studying molecular mechanisms of stress affecting immune response. [ABSTRACT FROM AUTHOR]

Circ_0007707 sequestered miR-27b-3p and subsequently elevated PDE3B expression in FLS-RA cells, thus promoting cell apoptosis and inflammatory response. [Display omitted] • Elevated expression of circ_0007707 was observed in synovial samples of RA patients. • Silencing of circ_0007707 induced cell apoptosis and decreased cell inflammatory response in FLS-RA cells. • Circ_0007707 sponged miR-27b-3p to regulate PDE3B expression. Synovial samples collected from 30 rheumatoid arthritis (RA) patients and 30 normal controls were used to isolate fibroblast-like synoviocytes (FLSs) and named FLS-RA and FLS-Normal, respectively. Real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to detect circ_0007707 expression. Effects of circ_0007707 silencing on cell proliferation and apoptosis were evaluated using cell counting kit-8, 5-ethynyl-2′-deoxyuridine (Edu), and flow cytometry assays. Levels of pro-inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). Increased circ_0007707 expression was observed in synovial samples from RA patients and FLS-RA cells. Functional analysis showed circ_0007707 silencing restrained cell proliferation, induced cell apoptosis, and decreased cell inflammatory response in FLS-RA cells. Mechanistic analysis revealed the sponge function of circ_0007707 on miR-27b-3p, and miR-27b-3p inhibition weakened circ_0007707 knockdown-mediated effects on FLS-RA cell proliferation, apoptosis, and inflammatory response. Circ_0007707 could mediate PDE3B expression via sponging miR-27b-3p, and PDE3B overturned miR-27b-3p mimic-mediated effects on FLS-RA cell proliferation, apoptosis, and inflammatory response. Circ_0007707 mediated cell apoptosis and inflammatory response in FLS-RA cells through the miR-27b-3p/PDE3B axis, indicating the potential function of circ_0007707 as a target for RA treatment. [ABSTRACT FROM AUTHOR]

Obesity, particularly increased visceral fat, positively correlates with various metabolic challenges, including atherosclerosis, but the mechanism is not fully understood. The aim of this study is to determine the role of visceral-fat-derived exosomes (Exo) in endothelial cells and atherosclerosis. We show that obesity changes the miRNA profile of visceral adipose exosomes in mice. Importantly, exosomal miR-27b-3p efficiently enters into the vascular endothelial cells and activates the NF-κB pathway by downregulating PPARα. Mechanistically, miR-27b-3p binds directly to the CDS region of PPARα mRNA, thereby promoting mRNA degradation and suppressing translation. In ApoE-deficient mice, administration of miR-27b-3p mimic increases inflammation and atherogenesis, while overexpression of PPARα protects against atherosclerosis. Thus, obesity-induced exosomal miR-27b-3p promotes endothelial inflammation and facilitates atherogenesis by PPARα suppression. We reveal an exosomal pathway by which obesity aggravates atherosclerosis and proposed therapeutic strategies for atherosclerosis in people with obesity. [Display omitted] • Obesity increases the level of exosomal miR-27b-3p in gonadal fat and plasma • miR-27b-3p promote endothelial inflammation and atherosclerosis in vitro and in vivo • The CDS region of PPARα is the miRNA-recognition elements of miR-27b-3p Tang et al. show that exosomal miR-27b-3p, derived from visceral adipocytes, is involved in endothelial inflammation and atherosclerosis. Mechanistically, miR-27b-3p binds directly to the CDS region of PPARα mRNA, thereby decreasing the protein expression. Overexpressing PPARα may be one therapeutic strategy for atherosclerosis in humans with obesity. [ABSTRACT FROM AUTHOR]

• IBDV infection upregulated gga-miR-27b-3p expression via demethylation of pre-miR-27 promoter in DF-1 cells. • gga-miR-27b-3p inhibited IBDV replication via enhancing the expressions of IFN-β, IRF3 and NF-κB. • gga-miR-27b-3p enhanced the mRNA expressions of STAT1, 3&6 by targeting SOCS3&6 during IBDV infection. • gga-miR-27b-3p acts as an anti-virus factor in host response against IBDV replication. MicroRNAs are small noncoding RNAs playing an important role in host response to pathogenic infection. Here we show that IBDV infection induced the demethylation of the pre-miR-27 promoter and upregulated gga-miR-27b-3p expression. We found that ectopic expression of miR-27b-3p in DF-1 cells enhanced the expression of chicken IFN-β, IRF3 and NF-κB, via directly targeting cellular suppressors of cytokine signaling 3 and 6 (SOCS3 and 6), inhibiting IBDV replication in host cells, while inhibition of endogenous miR-27b-3p by its inhibitors suppressed the expression of IFN-β, IRF3 and NF-κB, enhancing SOCS3 and 6 expressions and facilitating IBDV replication. Furthermore, transfection of DF-1 cells with miR-27b-3p markedly increased phosphorylation of STAT1 on Tyr701 in cells post chIFN-γ treatment. On the contrary, inhibition of endogenous miR-27b-3p reduced phosphorylation of STAT1 on Tyr701 in cells with chIFN-γ treatment. These findings indicate that gga-miR-27b-3p serves as an inducible antiviral mediator in host response to IBDV infection. [ABSTRACT FROM AUTHOR]

• PVT1 is highly expressed in osteoarthritis. • PVT1 knockdown increases cell viability and autophagy. • PVT1 knockdown decreases apoptosis and inflammatory response. • PVT1 acts a competing endogenous RNA for miR-27b-3p to derepress TRAF3. Long noncoding RNA plasmacytoma variant translocation 1 (PVT1) has been identified to implicate in the progression of osteoarthritis (OA). However, the mechanism underlying PVT1 in OA development remains largely unknown. This study aimed to investigate the effect of PVT1 on interleukin-1 beta (IL-1β)-induced injury in chondrocytes and explore potential mechanism. The cartilage tissues from 25 OA patients and normal controls were collected. Human transformed chondrocytes C28/I2 were stimulated by IL-1β. The levels of PVT1, microRNA (miR)-27b-3p, and tumor necrosis factor receptor-associated factor 3 (TRAF3) were detected by quantitative real-time polymerase chain reaction or western blot. IL-1β-induced injury was investigated by cell viability, apoptosis, autophagy and inflammatory response using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, flow cytometry, western blot and enzyme linked immunosorbent assay, respectively. The target association between miR-27b-3p and PVT1 or TRAF3 was explored by luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. We found that PVT1 expression was enhanced in OA patients and IL-1β-treated C28/I2 cells. Silence of PVT1 promoted cell viability and autophagy but suppressed apoptosis and inflammatory response in IL-1β-treated C28/I2 cells. miR-27b-3p was confirmed as a target of PVT1 and its deficiency reversed the suppressive effect of PVT1 knockdown on IL-1β-induced injury. TRAF3 was a target of miR-27b-3p and attenuated the effect of miR-27b-3p on IL-1β-induced injury in C28/I2 cells. Moreover, TRAF3 expression was positively regulated by PVT1 via sponging miR-27b-3p. Collectively, knockdown of PVT1 increased cell viability and autophagy but inhibited apoptosis and inflammatory response in chondrocytes treated by IL-1β via up-regulating miR-27b-3p and down-regulating TRAF3. [ABSTRACT FROM AUTHOR]

• MiR-27b-3p was downregulated in gastric cancer tissues and cells. • MiR-27b-3p can suppress gastric cancer cell proliferation, invasion, and migration. • MiR-27b-3p was downregulated by aberrant DNA methylation in gastric cancer. • GSPT1 was negatively regulated by miR-27b-3p via combining the 3′-untranslated region. Epigenetics play a vital role in the initiation and development of cancers, including gastric cancer (GC). In the present study, we aimed to explore potential up- and downstream mechanisms of miR-27b-3p in GC. The expression level of miR-27b-3p in GC cells and tissues (n = 80) was measured by quantitative RT-PCR. The mimics, inhibitors, and negative controls of miR-27b-3p were transfected into cell lines to perform the gain and loss of function study. Cell proliferation, migration, and invasion assays were utilized to assess biological behaviors caused by miR-27b-3p in vitro. Common target genes were predicted using four biological software programs and used for gene functional enrichment analysis. GSPT1 was selected for target gene verification using dual luciferase assays and its expression level was detected by western blot. The MKN-45 cell line was treated with 5-aza-2′-deoxycytidine (5-Aza-dC) and the methylation level was measured by methylation-specific PCR (MSP). miR-27b-3p was significantly downregulated in the GC cell lines and tissues compared with the normal group. The expression of miR-27b-3p was determined to be negatively associated with TNM stage and tumor size using statistical analysis. Overexpression of miR-27b-3p inhibited MKN-45 and SGC-7901 cell proliferation, invasion, and migration. Gene functional enrichment analysis indicated that the target genes were involved in several signaling pathways. Dual luciferase assays showed that miR-27b-3p combined with the 3′-untranslated region of GSPT1 mRNA. MSP demonstrated that miR-27b-3p promoter CpG island was hyper-methylated and 5-Aza-dC was able to partially reverse the methylation. Our study data indicated that miR-27b-3p is downregulated by aberrant DNA methylation in GC. In addition, miR-27b-3p suppresses GC cell proliferation, invasion, and migration via negative expression regulation of GSPT1, which could be a potential therapeutic target. [ABSTRACT FROM AUTHOR]