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长链非编码 RNA LINC01197 通过调控 miR-516b-5p/SIRT3/FOXO1 信号通路抑制草酸钙诱导的肾结石形成。

LncRNA LINC01197 inhibited the formation of calcium oxalate-induced kidney stones by regulating miR-516b-5p/SIRT3/FOXO1 signaling pathway.

机构信息

Department of Urology, The Second People's Hospital of Hefei (Hefei Hospital Affiliated to Anhui Medical University), No. 246 Heping Road, Hefei, 230011, Anhui, China.

The Fifth School of Clinical Medical of Anhui Medical University, Hefei, 230011, Anhui, China.

出版信息

Cell Tissue Res. 2023 May;392(2):553-563. doi: 10.1007/s00441-022-03734-6. Epub 2023 Jan 23.

Abstract

Long non-coding RNA (lncRNA) plays a key role in the regulation of calcium oxalate (CaOx) crystals-induced kidney stone formation and deposition. The purpose of this study is to study the effect of lncRNA LINC01197 on CaOx-induced kidney stone formation and the underlying mechanism. Crystal cell adhesion in HK-2 cells was evaluated by analyzing Ca2+ concentration. Apoptosis was detected by flow cytometry. The RT-qPCR and western blot were used to detect the mRNA and protein expression. Patients with kidneys stones showed down-regulated LINC01197 and SIRT3 expression, and up-regulated miR-516b-5p expression. LINC01197 knockdown promoted CaOx-induced cell adherence and cell apoptosis, increased Bax, decreased Bcl-2 expression. Luciferase reporter assay showed that SIRT3 expression was promoted by LINC01197 competing binds to miR-516b-5p. In addition, LINC01197 expression was promoted by SIRT3/FOXO1 overexpression, and could be reversed by FOXO1 knockdown. In conclusion, the present study revealed that lncRNA LINC01197 inhibited CaOx-induced kidney stones formation by regulating the miR-516b-5p/SIRT3/FOXO1 signaling pathway.

摘要

长链非编码 RNA(lncRNA)在调节草酸钙(CaOx)晶体诱导的肾结石形成和沉积中起着关键作用。本研究旨在研究 lncRNA LINC01197 对 CaOx 诱导的肾结石形成的影响及其潜在机制。通过分析 Ca2+浓度来评估 HK-2 细胞中的晶体细胞黏附。通过流式细胞术检测细胞凋亡。采用 RT-qPCR 和 Western blot 检测 mRNA 和蛋白表达。肾结石患者的 LINC01197 和 SIRT3 表达下调,miR-516b-5p 表达上调。LINC01197 敲低促进 CaOx 诱导的细胞黏附和细胞凋亡,增加 Bax,减少 Bcl-2 表达。荧光素酶报告实验表明,LINC01197 通过与 miR-516b-5p 竞争结合来促进 SIRT3 表达。此外,SIRT3/FOXO1 过表达促进 LINC01197 表达,而 FOXO1 敲低可逆转这一作用。总之,本研究揭示了 lncRNA LINC01197 通过调节 miR-516b-5p/SIRT3/FOXO1 信号通路抑制 CaOx 诱导的肾结石形成。

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