Hsa‑miR‑371‑5p inhibits human mesangial cell proliferation and promotes apoptosis in lupus nephritis by directly targeting hypoxia‑inducible factor 1α.

Feifei Yao, Liqiu Sun, Wei Fang, Huamin Wang, Dongsheng Yao, Rui Cui, Jia Xu, Li Wang, Xiumei Wang

Molecular medicine reports 2016 Dec

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MicroRNAs (miRNAs/miR) have emerged as a novel class of gene expression modulators in kidney disease. Lupus nephritis (LN) is the predominant cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Hsa‑miR‑371‑5p has previously been reported to be dysregulated in LN using a miRNA microarray analysis. The present study aimed to determine the function and molecular mechanisms of hsa‑miR‑371‑5p in human mesangial cells of LN. Quantitative polymerase chain reaction (qPCR) was used to detect hsa‑miR‑371‑5p expression in LN tissues. Furthermore, the MTT assay and flow cytometric analyses were performed to analyze the effects of hsa‑miR‑371‑5p on mesangial cell proliferation and apoptosis. Bioinformatics analysis, luciferase reporter assay, qPCR and western blotting were also conducted to predict and confirm the target gene of hsa‑miR‑371‑5p in mesangial cells. The results demonstrated that hsa‑miR‑371‑5p expression was markedly downregulated in LN renal tissues compared with in normal kidney tissues. Restoration of hsa‑miR‑371‑5p expression using synthetic hsa‑miR‑371‑5p mimics was able to significantly inhibit mesangial cell proliferation and induce apoptosis. In addition, mechanistic exploration demonstrated that hypoxia‑inducible factor 1α (HIF‑1α) was a direct target gene of hsa‑miR‑371‑5p in mesangial cells. In conclusion, these results suggested that hsa‑miR‑371‑5p is downregulated in LN, and overexpression of hsa‑miR‑371‑5p may inhibit mesangial cell proliferation and promote apoptosis by directly targeting HIF‑1α.

Citation

Feifei Yao, Liqiu Sun, Wei Fang, Huamin Wang, Dongsheng Yao, Rui Cui, Jia Xu, Li Wang, Xiumei Wang. Hsa‑miR‑371‑5p inhibits human mesangial cell proliferation and promotes apoptosis in lupus nephritis by directly targeting hypoxia‑inducible factor 1α. Molecular medicine reports. 2016 Dec;14(6):5693-5698