Effects of long non-coding RNA LINC00667 on renal tubular epithelial cell proliferation, apoptosis and renal fibrosis via the miR-19b-3p/LINC00667/CTGF signaling pathway in chronic renal failure

Abstract

The global prevalence of chronic renal failure (CRF) has significantly elevated with various reports indicating there to be a 10% worldwide rate. The functions of long non-coding RNAs (lncRNAs) and their deeper association with CRF at present remain poorly understood. Hence, the aim of the present study was to investigate the altered expressions of lncRNA LINC00667 in CRF and its associated effects on renal tubular epithelial cell proliferation, apoptosis and renal fibrosis through the microRNA-19b-3p (miR-19b-3p)/LINC00667/connective tissue growth factor (CTGF) signaling pathway. Initially, verification of the targeting relationship between LINC00667, CTGF and miR-19b-3p was performed, after which evidence was obtained indicating that miR-19b-3p could negatively regulate LINC00667 and CTGF. The expressions of CTGF in both the CRF and normal renal tissues were determined by immunohistochemistry means, with LINC00667 and CTGF determined to be highly expressed, while poor expression levels of miR-19b-3p were detected among the CRF tissues. The expressions of LINC00667, miR-19b-3p, fibrosis- and epithelial-mesenchymal transition (EMT)-related genes were also examined. The successfully established CRF rat models were treated with varying mimics, inhibitors, and siRNA. ELISA was applied to determine the renal function-related factors. Besides, the renal cell proliferation, migration and apoptosis were detected. In response to LINC00667 silencing, the renal tubular epithelial cells displayed increased proliferation and migration accompanied by reduced apoptosis based on upregulated miR-19b-3p, along with inhibited renal fibrosis and EMT detected. Taken together, the key findings of our study demonstrated that decreased lncRNA LINC00667 could promote renal tubular epithelial cell proliferation and ameliorate renal fibrosis in CRF via the miR-19b-3p/LINC00667/CTGF signaling pathway.

Keywords: CTGF; Chronic renal failure; Long non-coding RNA LINC00667; MiR-19b-3p; Renal fibrosis.