MiRNA-155 Regulates the Th17/Treg Ratio by Targeting SOCS1 in Severe Acute Pancreatitis

Abstract

Acute pancreatitis (AP) is a serious condition associated with intestinal barrier disruption or inflammation of the pancreatic tissue. Specific microRNAs are involved in the pathogenesis of AP, during which IL-17-producing CD4+ T helper (Th17) cells accumulate in the pancreas. In this study, significantly increased levels of miR-155 were detected in clinical samples from patients with AP, and overexpression of miR-155 correlated with severe AP (SAP). To identify the effect of miR-155 on T cell differentiation, we isolated CD4+ T lymphocytes and in vitro experiments showed that inhibition of miR-155 significantly reversed the stress-induced increase in the Th17/Treg ratio. The results also showed that miR-155 increased the Th17-mediated inflammatory response by targeting SOCS1. The interaction between miR-155 and the 3′-UTR of SOCS1 was confirmed by a dual luciferase reporter assay and RT-PCR. Experimental AP of varying severity was induced in BALB/c mice by caerulein hyperstimulation and miR-155 expression was found to increase with disease progression. Inhibition of miR-155 expression significantly improved the pathology of the pancreas. We also observed downregulation of expression of inflammatory factors, IL-17, SOCS1 and phosphorylated STAT1 after miR-155 inhibition. In summary, miR-155 regulates the Th17/Treg ratio by targeting SOCS1, most probably via direct binding to its 3′-UTR region, indicating that this microRNA may be a potential biomarker and/or therapeutic target for AP.

Effect of gga-miR-155 on cell proliferation, apoptosis and invasion of Marek’s disease virus (MDV) transformed cell line MSB1 by targeting RORA

“…It is also a tumor suppressor and therefore inactivated during malignant transformation, and tumor initiation and metastasis [47,48]. Several targets of miRNA-155 have been identified in recent years, such as the BRG1 [49] and FOXO3a [50] in lymphoma, and SOCS1 in severe acute pancreatitis [51]. Parnas et al predicted 9 common target genes of MDV1-miR-M4, KSHV-miR-K11 and HAS-miR-155, and 4 of MDV1-miR-M4 and HAS-miR-155 in human B cells and chicken T cells, which includes RORA [32].…”

Luteolin Inhibits Respiratory Syncytial Virus Replication by Regulating the MiR-155/SOCS1/STAT1 Signaling Pathway

“…regulators of effector CD8(+) T cells as they affect cytokine signaling through STAT5 (Dudda et al, 2013). Wang et al found that in acute pancreatitis, miR-155 targets SOCS1 to regulate the Th17 cell/Treg ratio, thus mediating disease severity (Wang et al, 2018). MiR-155 was also shown to function as a proproliferative regulator during liver regeneration by facilitating the cell cycle and directly targeting SOCS1 (Lin et al, 2018).…”

Effect of gga-miR-155 on Cell Proliferation, Apoptosis and invasion of Marek’s disease Virus (MDV) transformed cell line MSB1 by targeting RORA

“…It is also a tumor suppressor and therefore inactivated during malignant transformation, and tumor initiation and metastasis [47,48] . Several targets of miRNA-155 have been identified in recent years, such as the BRG1 [49] and FOXO3a [50] in lymphoma, and SOCS1 in severe acute pancreatitis [51] . Parnas et al predicted 9 common target genes of MDV1-miR-M4, KSHV-miR-K11 and HAS-miR-155, and 4 of MDV1-miR-M4 and HAS-miR-155 in human B cells and chicken T cells, which includes RORA [32] .…”