Department of Nephrology, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China (mainland).
Department of Nephrology, Second Affiliated Hospital of Nanchang Universityy, Nanchang, Jiangxi, China (mainland).
Med Sci Monit. 2020 Feb 13;26:e919415. doi: 10.12659/MSM.919415.
BACKGROUND CASC15 has been recently characterized as an oncogenic lncRNA. This study aimed to investigate the role of CASC15 in diabetic patients complicated with chronic renal failure (DCRF). MATERIAL AND METHODS Levels of CASC15 in plasma derived from 3 groups of participants were measured by qPCR and compared by ANOVA and Tukey test. The interaction between CASC15 and miR-34c was analyzed by performing cell transfections. Cell apoptosis assay was performed to analyze the effects of transfections on the apoptosis of CIHP-1 cells (podocytes). RESULTS We found that CASC15 in plasma was upregulated in DCRF compared with diabetic patients (no obvious complications) and healthy controls. Upregulation of CASC15 distinguished DCRF patients from healthy controls and diabetic patients. High D-glucose environment induced the upregulation of CASC15 in cells of the human podocyte cell line CIHP-1. Overexpression of CASC15 did not affect miR-34c in CIHP-1 cells, but bioinformatics analysis showed that CASC15 can sponge miR-34c. Overexpression of CASC15 led to an increased apoptotic rate of CIHP-1 cells, and miR-34c overexpression led to a decreased apoptotic rate of CIHP-1 cells. In addition, CASC15 overexpression attenuated the effects of miR-34c overexpression on cell apoptosis. CONCLUSIONS Therefore, CASC15 is upregulated in DCRF patients and promotes the apoptosis of podocytes by sponging miR-34c. Our study adds to our understanding of the pathogenesis of DCRF and suggests that CASC15 could serve as a potential therapeutic target of DCRF.
CASC15 最近被鉴定为一种致癌的 lncRNA。本研究旨在探讨 CASC15 在合并慢性肾衰竭（DCRF）的糖尿病患者中的作用。
通过 qPCR 测量来自 3 组参与者的血浆中的 CASC15 水平，并通过 ANOVA 和 Tukey 检验进行比较。通过进行细胞转染分析 CASC15 和 miR-34c 之间的相互作用。进行细胞凋亡测定以分析转染对 CIHP-1 细胞（足细胞）凋亡的影响。
我们发现与糖尿病患者（无明显并发症）和健康对照相比，血浆中的 CASC15 在 DCRF 中上调。CASC15 的上调将 DCRF 患者与健康对照和糖尿病患者区分开来。高 D-葡萄糖环境诱导人足细胞系 CIHP-1 细胞中 CASC15 的上调。在 CIHP-1 细胞中，CASC15 的过表达不影响 miR-34c，但生物信息学分析表明 CASC15 可以海绵 miR-34c。CASC15 的过表达导致 CIHP-1 细胞的凋亡率增加，而过表达 miR-34c 导致 CIHP-1 细胞的凋亡率降低。此外，CASC15 的过表达减弱了 miR-34c 过表达对细胞凋亡的影响。
因此，CASC15 在 DCRF 患者中上调，并通过海绵 miR-34c 促进足细胞的凋亡。我们的研究增加了我们对 DCRF 发病机制的理解，并表明 CASC15 可能成为 DCRF 的潜在治疗靶点。
