Circ_0068087 Promotes High Glucose-Induced Human Renal Tubular Cell Injury through Regulating miR-106a-5p/ROCK2 Pathway

Abstract

<b><i>Background:</i></b> Many studies have confirmed that circular RNA (circRNA) is an important target for regulating human disease progression. This study aimed to explore the role of circ_0068087 in diabetic nephropathy (DN) progression. <b><i>Methods:</i></b> High glucose (HG)-induced renal tubular cells (HK2) were used to mimic DN cell models in vitro. The expression levels of circ_0068087, microRNA (miR)-106a-5p, and Rho-associated coiled-coil-containing kinase 2 (ROCK2) were detected by quantitative real-time PCR. Cell proliferation and apoptosis were examined by cell counting kit-8 assay, 5-ethynyl-2′-deoxyuridine assay, colony formation assay, and flow cytometry. The protein levels were examined by Western blot analysis. Cell oxidative stress was assessed by measuring MDA level and SOD activity, and cell inflammation was evaluated by detecting the concentrations of inflammatory factors. RNA interaction was verified by dual-luciferase reporter assay and RNA pull-down assay. <b><i>Results:</i></b> The present study showed that circ_0068087 was highly expressed in the serum of DN patients and HG-induced HK2 cells. Interference of circ_0068087 alleviated HG-induced apoptosis, oxidative stress, inflammation, and fibrosis in HK2 cells, while accelerated cell proliferation. miR-106a-5p could be sponged by circ_0068087, and its inhibitor eliminated the regulation of circ_0068087 knockdown on HG-induced HK2 cell injury. ROCK2 was a target of miR-106a-5p, and its expression was suppressed by circ_0068087 knockdown. miR-106a-5p overexpression suppressed HG-induced HK2 cell injury, and this effect was reversed by ROCK2 upregulation. <b><i>Conclusion:</i></b> Our data indicated that circ_0068087 downregulation mitigated HG-induced HK2 cell injury through the miR-106a-5p/ROCK2 axis, providing a potential circRNA-targeted therapy for DN.

Adipose‐derived miRNAs as potential biomarkers for predicting adulthood obesity and its complications: A systematic review and bioinformatic analysis

“…miR‐181a‐5p protects against myocardiocyte apoptosis by targeting programmed cell death 4 in diabetic cardiomyopathy. miR‐24, miR‐106a and miR‐130a‐3p alleviate hyperglycemia‐induced podoplanin cellular inflammation and apoptosis in diabetic nephropathy 116–118 . miR‐17‐5p and miR‐24 protect against hyperglycemia‐induced endothelial cell damage and enhance autophagy in DM‐associated endothelial dysfunction 119,120 .…”

“…The early onset of metabolic disorders often goes undetected. Dysregulated miRNA expression may be implicated in T2DM pathogenesis and could be a diagnostic marker for T2DM and its associated compli- and miR-130a-3p alleviate hyperglycemia-induced podoplanin cellular inflammation and apoptosis in diabetic nephropathy [116][117][118] . miR-17-5p and miR-24 protect against hyperglycemia-induced endothelial cell damage and enhance autophagy in DM-associated endothelial dysfunction 119,120 .…”

Circular RNAs and the regulation of gene expression in diabetic nephropathy (Review)

“…2 and Table SI ). Most of the remaining circRNAs listed in Table SI regulate molecules involved in inflammation, apoptosis, oxidative stress and fibrosis via other signaling pathway ( 29 , 81 - 104 ). CircRNA_ANKRD36, hsa_circRNA_0001831 and hsa_ circRNA_0000867 have been shown to be upregulated in blood samples of patients with DN; however, their targets and mechanisms of action remain unknown ( 105 , 106 ) ( Table SI ).…”