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

Abstract

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.

Characterization of a Novel LUCAT1/miR-4316/VEGF-A Axis in Metastasis and Glycolysis of Lung Adenocarcinoma

“…This study proved that high glucose conditions could enhance the ability of migration and invasion in LUAC cells. Lin and colleagues found that LUCAT1 was upregulated under high-glucose conditions, and knockdown of LUCAT1 inhibited the EMT in HG-treated HK-2 cells (Zhang et al, 2020). Therefore, we assumed that LUCAT1 might regulate migration and invasion of LUAD cells by participating in the process of glucose metabolism.…”

“…Recently, growing evidence have provided for cancer cells' dependent on glycolysis for energy production (Vander Heiden et al, 2009). It was reported that LUCAT1 was upregulated under high-glucose conditions, and knockdown of LUCAT1 inhibited the EMT in HG-treated HK-2 cells (Zhang et al, 2020), however, whether LUCAT1 participate in glycolysis of LUAD cells needs to be confirmed.…”

Changes in Exosomal miRNA Composition in Thyroid Cancer Cells after Prolonged Exposure to Real Microgravity in Space

“…The authors demonstrated modulation of EMT genes and stem cancer markers and suspect that miR-199a-5p may be involved in chemotherapy sensitivity in TNBC [ 146 ]. Further, through targeting ZEB1, miR-199a-5p inhibits EMT of ovarian ectopic endometrial stromal cells via the PI3K/Akt/mTOR signal pathway and in human renal tubular epithelial cells [ 147 , 148 ].…”

LncRNA CDKN2B‐AS1 contributes to glioma development by regulating the miR‐199a‐5p/DDR1 axis

“…Our study confirmed that miR‐199a‐5p and DDR1 axis also play important roles in glioma progression. Other mRNAs have also been identified as the targets of miR‐199a‐5p, including NRP1 in sepsis, 31 Klotho in gastric cancer, 32 and ZEB1 in human renal tubular epithelial cells 33 . Further experiments should be performed to investigate the regulatory axis of miR‐199a‐5p and these potential mRNA targets in glioma.…”