miRNA‑125a modulates autophagy of thyroiditis through PI3K/Akt/mTOR signaling pathway

Abstract

The present study examined the potential function and underlying mechanisms of microRNA-125a (miR-125a) in thyroiditis. Mice were subcutaneously administered with 100 µg porcine thyroglobulin weekly for 2 weeks to establish the thyroiditis model. Results of the in vivo study demonstrated that miR-125a serum expression was upregulated in thyroiditis mice compared with the control group. In vitro studies were performed on a mouse macrophage cell line in which a model of thyroiditis was established using 10 ng/ml human interferon-γ. Upregulated miR-125a expression was achieved via mimic transfection. Increased miR-125a expression reduced autophagy and cell proliferation, increased the apoptotic rate and the expression of pro-inflammatory factors tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-18 via downregulation of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. PI3K inhibition enhanced the ability of miR-125a to increase the inflammatory response in vitro via regulation of the PI3K/Akt/mTOR signaling pathway. These results suggest miR-125a inhibited autophagy in a model of thyroiditis through the PI3K/Akt/mTOR signaling pathway.

Elevated circulating lnc‐ANRIL/miR‐125a axis level predicts higher risk, more severe disease condition, and worse prognosis of sepsis

“…These mechanistic experiments indicate that miR‐125a is a crucial regulator in inflammation and immune responses, which might explain the results in our study that miR‐125a plasma expression could predict sepsis risk, and was negatively correlated with severity and pro‐inflammatory cytokines levels in sepsis patients. In addition, there is a report showing that U6 might not be an appropriate internal reference for miRNAs detection; however, for circulating miR‐125a expression detection, there are still mounting studies using U6 as an internal reference …”

“…Univariate and multivariate Cox's proportional hazards model analyses of factors affecting accumulating survival sepsis risk, and was negatively correlated with severity and pro-inflammatory cytokines levels in sepsis patients. In addition, there is a report showing that U6 might not be an appropriate internal reference for miRNAs detection; however, for circulating miR-125a expression detection, there are still mounting studies using U6 as an internal reference 12,[30][31][32].…”

Measurement of circulating miRNA‐125a exhibits good value in the management of etanercept‐treated psoriatic patients

“…14 In another study, miR-125a expression is reduced in systemic lupus erythematosus compared with HC, and its overexpression inhibits the levels of inflammatory chemokines ROC and AUC as well as the sensitivity and specificity at median value of the variable were used to assess the feasibility of the variable in distinguishing different subjects. 15,16,21 For example, increased miR-125a expression reduces cell proliferation but increases the apoptotic rate through downregulating the PI3K/Akt signaling pathway in thyroiditis. AUC, area under the curve; CI, confidence interval; HC, healthy controls; miR-125a, miRNA-125a; ROC, receiver-operating curve.…”

“…P < 0.05 was considered significant. 21 Another study indicates that overexpression of miR-125a reduces human umbilical vein endothelial cell proliferation and viability through downregulating antiapoptotic Bcl2 protein and upregulating caspase 3. by regulating the expression of its potential target gene KLF13 in vitro.…”

“…12 In addition, several evidences indicate the association of miR-125a with cell proliferation in inflammatory-related diseases. 15,16,21 For example, increased miR-125a expression reduces cell proliferation but increases the apoptotic rate through downregulating the PI3K/Akt signaling pathway in thyroiditis. 21 Another study indicates that overexpression of miR-125a reduces human umbilical vein endothelial cell proliferation and viability through downregulating antiapoptotic Bcl2 protein and upregulating caspase 3.…”