Let-7c-5p Is Involved in Chronic Kidney Disease by Targeting TGF- β Signaling.

The purpose of the present study was to investigate the expressions of hsa-let-7c-5p and TGF-beta signaling-related molecules and their correlations with clinical characteristics in chronic kidney disease (CKD). Twenty-three biopsy specimens of CKD patients and 20 negative control tissues were selected. Quantitative real-time PCR (qPCR) was used for the detection of hsa-let-7c-5p, transforming growth factor beta (TGF-beta) and TGF-beta receptor type 1 (TGF-beta R1) expression levels. Target gene of hsa-let-7c-5p was verified by dual-luciferase reporter assay. A significant decrease of hsa-let-7c-5p expression in CKD tissue was found, compared with that of normal renal tissues (p<0.01). Expression levels of TGF-beta in CKD were increased, compared with that of normal kidney tissue (p<0.001). The difference in the expression of TGF-beta R1 between CKD tissues and normal renal tissues was not significant (p>0.05). A negative correlation was found between the expression of TGF-beta and renal tissue hsa-let-7c-5p levels. Furthermore, hsa-let-7c-5p was identified to regulate TGF-beta 1 by directly binding with the 167-173 site in the 3 ' untranslated region. Decreased hsa-let-7c-5p levels in CKD patients was found to be associated with disease severity, which shows a negative correlation with proteinuria and creatinine levels, and a positive correlation with estimated glomerular filtration rate (eGFR), while relative TGF-beta 1 expression had a positive correlation with creatinine level. In summary, changes in hsa-let-7c-5p expression and its target gene TGF-beta are associated with the disease status of CKD. Let-7c-5p may contribute to the pathogenesis of renal fibrosis through TGF-b signaling, a potential diagnostic and therapeutic target of the disease.