Circulating microRNA expression profile and clinical significance of circulating miR-130b-3p in patients with lupus nephritis

Abstract

Objective To analyze the changes of circulating miRNAs expression and explore their possible significance in patients with lupus nephritis (LN) at different stages. Methods There were a total of 94 serum samples from 58 LN patients and 36 healthy controls. 12 serum samples selected that were comparable in gender and age were used to analyze the expression profile of circulating miRNAs with PCR array, including serum samples (n=4 in each group) from healthy control, early stage LN patients (CKD 1-3 stage), and late stage LN patients (CKD 4-5 stage); and the other 50 LN patients were used as the validation group, including 40 cases of early LN patients, and 10 late LN patients. The Nanodrop 2000 was were determined by the Spearman rank correlation coefficient. Results The used for detecting RNA concentration. Two miRNAs, miR-130b-3p and miR-1233-3p were selected as to be validated. Correlations expressions of seven miRNAs, including miR-1233-3p (P=0.019), miR-130b-3p (P=0.021), miR-18a-3p (P=0.021), miR-628-3p (P=0.023), miR-1260b (P=0.030), miR-1539 (P=0.041), and miR-378e (P=0.047) were increased in early stage LN patients compared with the healthy controls. On the other hand, the expression levels of most circulating miRNAs were found decreased in late stage LN patients, and no circulating miRNAs were found up-regulated more than 2 times or increased significantly compared to those in the healthy controls or early LN patients; the tatol serum RNA was reduced in late LN patients of validation group compared to that in healthy controls (P<0.001, U=4.5) or early LN patients (P<0.001, U=18.0); the level of miR-130b-3p was significantly higher in early stage LN patients compared to healthy controls [IQR 16.2 (8.7, 42.7) vs 9.6 (4.8, 17.4), P=0.008, U=405.5)], and decreased significantly in late stage LN group compared to healthy controls (U=69.0, P=0.008) or early LN patients (U=46.0, P<0.001). The miR-1233-3p also significantly down-regulated in late stage LN group compared to healthy controls (U=80.0, P=0.019) or early LN patients (U=70.0, P=0.002). The expression of serum miR-130b-3p was significantly and positively correlated with 24-hour proteinuria (r=0.404, P=0.010), chronicity index (r=0.389, P=0.013), and serum triglyceride level (r=0.376, P=0.017). Conclusions The circulating miRNA levels were reduced in patients with severe chronic renal failure. MiR-130b-3p was up-regulated in early stage LN patients, and associated with renal injury and abnormal regulation of serum lipids, playing a possible role in the development and progression of LN. Key words: Systemic lupus erythematosus; Lupus nephritis; Chronic kidney disease; Epigenetic regulation; MicroRNA