Abstract
microRNAs (miRs) are short non-coding RNAs that function as guide molecules in RNA silencing by inducing mRNA degradation or blocking protein translation. Increasing evidence has shown that miRNAs play an important role in regulating the pathological process of lupus nephritis (LN), but the precise role of miR-124 in LN is still unknown. Here, we found that miR-124 expression is significantly reduced in patients with active LN compared with those patients with non-active LN and the absence of LN. Additionally, the miR-124 level was negatively correlated with serum IL-1β, IL-6, TNF-α, and TRAF6 mRNA expressions in active LN patients. Receiver operating characteristic and logistic regression analyses revealed miR-124 is a significant diagnostic biomarker for active LN. Furthermore, transfection of the miR-124 mimic into human renal mesangial cells (HRMCs) resulted in significantly reduced cell proliferation, induced cell apoptosis, and decreased synthesis of inflammatory factors. Moreover, a dual luciferase assay showed that TRAF6 was a direct target of miR-124, and the expression of TRAF6 was suppressed by miR-124 through direct binding to the 3'-UTR of mRNA. Mechanistic studies demonstrated that the over-expression of TRAF6 could abrogate miR-124-related effects on cell proliferation, apoptosis and the synthesis of inflammatory factors in HRMCs. Taken together, these findings indicate that downregulated miR-124 represents a novel diagnostic marker in human LN and plays an inhibitory effect on the growth and inflammation of renal mesangial cells by targeting TRAF6.