miR-148a-3p overexpression contributes to glomerular cell proliferation by targeting PTEN in lupus nephritis

Abstract

The objective of this study was to investigate the role of miR-148a-3p in lupus nephritis (LN) based on data from previous studies and a microRNA assay. We evaluated the miR-148a-3p expression level in LN renal tissues and blood serum to determine its clinicopathological significance and effect on glomerular cell proliferation. Then, we collected renal glomeruli from LN mice and determined the miR-148a-3p, proliferating cell nuclear antigen (PCNA), and PCNA/Thy1 expression. We performed functional analyses of miR-148a-3p in vitro and in vivo. We also investigated the target gene of miR-148a-3p in LN. The results showed that miR-148a-3p expression levels were significantly higher not only in glomeruli but also in the blood serum during LN and increased in the glomeruli of LN mice and that at the same time there was positive correlation between miR-148a-3p and PCNA expression of glomruli. Overexpression of miR-148a-3p accelerated cell proliferation and PCNA expression, while a miR-148a-3p inhibitor inhibited cell proliferation via the Akt/cyclin D1 pathway. Furthermore, miR-148a-3p overexpression reduced the phosphatase and tensin homology deleted on chromosome ten (PTEN) expression level, while miR-148a-3p silencing increased its expression in high-mobility group box 1 (HMGB1)-induced mouse mesangial cells (MMCs). Luciferase assays demonstrated that miR-148a-3p could directly bind to the PTEN 3'-UTR. PTEN overexpression inhibited MMC proliferation considerably, resembling the results observed during miR-148a-3p inhibition. Reducing miR-148a-3p expression upregulated PTEN in the glomeruli and improved renal function in LN mice. Thus miR-148a-3p may promote proliferation and contribute to LN progression by targeting PTEN.

Circulating microRNA signatures serve as potential diagnostic biomarkers for Helicobacter pylori infection

“…miR‐151‐3p functions as a key regulator in epithelial‐to‐mesenchymal transition (EMT), innate immunity, and inflammation, which is concordant with the fact that H pylori infection unavoidably triggers immune response and inflammation. In addition, miR‐148a‐3p played important roles in restraining cell proliferation and EMT . Taken together, these facts indicate that H pylori infection involves in multiple biological processes that are collectively mediated by these miRNAs.…”

“…In addition, miR-148a-3p played important roles in restraining cell proliferation and EMT. [31][32][33] Taken together, these facts indicate that H pylori infection involves in multiple biological processes that are collectively mediated by these miRNAs.…”

Plasma microRNA signature is associated with risk stratification in prostate cancer patients

“…26 In this regard, Qingjuan et al recently reported that miR-148a could directly bind to the 3 0 -UTR of PTEN and reduce the expression of PTEN in lupus nephritis, resulting in accelerated glomerular cell proliferation and tumor progression. 27 However, to introduce miRNAs into the clinical practice, more research is needed to identify their target mRNAs and understand their functions, as they harbor both oncogenic and tumor suppressive characteristics. The different features of miRNAs suggest that they act on multiple targets in different cellular processes that contribute to PCa development and progression.…”

MicroRNA-148a Regulates Low-Density Lipoprotein Metabolism by Repressing the (Pro)renin Receptor

“…It would be interesting to explore whether miR-148a could, by modulating (P)RR-mediated functions, such as regulating lipid metabolism, maintaining V-ATPase integrity, and activating tissue RAS, contribute to the onset and progression of such diseases. Among these diseases, it is interesting to notice that plasma miR-148a levels were elevated in LN patients and mice [37]. LN patients have higher risks for ischemic heart diseases [38,39], which is likely caused by abnormalities in lipid metabolism.…”