肾结石是一种反复发作且伴随终生的疾病，临床治疗效果不理想。我们的前期研究证实SIRT3能够通过促进FOXO1去乙酰化抑制肾结石形成，并经预实验证实LINC01197可能在该病的病理进展中发挥重要作用。在此申请者提出：LINC01197作为miRNA海绵，与SIRT3mRNA竞争结合miR-516b-5p，以促进SIRT3表达并诱导FOXO1去乙酰化，去乙酰化的FOXO1则促进LINC01197表达，LINC01197通过miR-516b-5p/SIRT3/FOXO1反馈回路参与调节肾结石发展。本项目拟首先在临床、动物与细胞水平确定关键因子在结石肾中的表达，然后通过设计功能获得与缺失实验及挽救实验，应用免疫组化等手段明确LINC01197/miR-516b-5p/SIRT3/FOXO1反馈回路在肾结石发生发展中的作用，通过本项目的研究揭示新的肾结石病理机制，为该病的治疗提供新的治疗靶点。

Kidney stone is usually a recurring and lifelong disease, has a poor curative effect. It is important to explore the molecular action mechanism of the disease and explore new treatment targets. Our previous studies confirmed that SIRT3 could inhibit kidney stone formation by promoting FOXO1 deacetylation. Meanwhile, our pre-experiment data revealed that the long non-coding RNA LINC01197 may be play a crucial role in the development of kidney stone. In this project, the applicant proposed the following scientific hypothesis: LINC01197 competes with SIRT3 mRNA to bind with miR-516b-5p and promotes SIRT3 expression via acting as a miRNA sponge, and then induces FOXO1 deacetylation, however, deacetylated FOXO1 further promotes LINC01197 expression. Thus, LINC01197 regulates the development of kidney stones through involving in the miR-516b-5p/SIRT3/FOXO1 feedback loop. In order to verify the establishment of this hypothesis, the expression differences of key factors of this project under physiological and pathological conditions are first determined at clinical, animal and cell level. Subsequently, experimental tools such as overexpression plasmids, mimics, siRNA and lentivirus are used to conditionally determine the expression levels of LINC01197, miR-516b-5p, and SIRT3 in animal models and cells, meanwhile, immunohistochemistry, western blot, qRT-PCR, TUNEL, and HE staining are used to determine the key indicators in the development of kidney stones. Finally, the regulation effect of LINC01197/miR-516b-5p/SIRT3/FOXO1 feedback loop in the occurrence and development of kidney stones is clarified. The research of this project will reveal new pathological mechanisms of kidney stones and provides new therapeutic targets for the treatment of this disease.