Knockdown of the Long Noncoding RNA LUCAT1 Inhibits High-Glucose-Induced Epithelial-Mesenchymal Transition through the miR-199a-5p–ZEB1 Axis in Human Renal Tubular Epithelial Cells

• Published in: BioMed research international Vol. 2020; no. 2020; pp. 1 - 8
• Main Authors: Zhang, Li-Cai, Tang, Shui-Fu, Wei, Zong-Bin
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 2020; Hindawi; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Analysis; Antisense RNA; Biomedical research; Cell adhesion & migration; Cell culture; Chronic kidney failure; Clear cell-type renal cell carcinoma; Complications and side effects; Cystic fibrosis; Diabetes; End-stage renal disease; Epithelial cells; Fibrosis; Genetic aspects; Glucose; Investigations; Kidney diseases; Lung cancer; Mesenchyme; Methods; MicroRNA; MicroRNAs; miRNA; Pathogenesis; Phosphorylation; Physiological aspects; Polymerase chain reaction; Prevention; Proteins; Regulatory sequences; Reverse transcription; Ribonucleic acid; Risk factors; RNA; RNA sequencing; siRNA; Smad3 protein; China; United States > US
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2020/8895003

Renal fibrosis, the leading cause of end-stage renal disease and in which epithelial-mesenchymal transition (EMT) plays a central role, has a complex pathogenesis that is not fully understood. Therefore, we investigated the role of the long noncoding RNA LUCAT1 in the EMT of renal tubular epithelial cells under high-glucose (HG) conditions and the underlying mechanism involved. In this study, we established HG and normal glucose groups of HK-2 cells by treating HK-2 cells 30.0 or 5.5 mmol/L glucose, respectively. To investigate the roles of LUCAT1 and miR-199a-5p in HG-induced EMT, we transfected the HG group with negative control small interfering RNA (siRNA), siRNA targeting LUCAT1, negative control microRNA, or an miR-199a-5p mimic. The results of the quantitative reverse transcription PCR indicated that the LUCAT1 level in the HG group was increased, whereas the miR-199a-5p level was decreased. The EMT in the cells was induced by treatment with HG but was weakened by LUCAT1 knockdown or miR-199a-5p overexpression, which both also inhibited the HG-induced phosphorylation of SMAD3. Moreover, LUCAT1 and ZEB1 mRNA comprised the same microRNA response elements of miR-199a-5p. LUCAT1 knockdown had no effect on the miR-199a-5p level but decreased the HG-induced upregulation of ZEB1. In conclusion, HG conditions induced the upregulation of LUCAT1, and LUCAT1 knockdown inhibited the EMT in HG-treated HK-2 cells. LUCAT1 likely promotes HG-induced EMT through ZEB1 by sponging miR-199a-5p.