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miR-29a-3p 通过靶向磷酸酶张力蛋白同源物抑制骨关节炎进展。

MiR-29a-3p mediates phosphatase and tensin homolog and inhibits osteoarthritis progression.

机构信息

Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou City, 646000, Sichuan Province, China.

Department of Orthopedics, Chinese Medicine Hospital of Anyue County, Ziyang City, 642350, Sichuan Province, China.

出版信息

Funct Integr Genomics. 2024 Mar 12;24(2):54. doi: 10.1007/s10142-024-01327-w.

DOI:10.1007/s10142-024-01327-w
PMID:38467932
Abstract

Despite substantial progress in clinical trials of osteoarthritis (OA) gene therapy, the prevalence of OA is still on the rise. MiRNAs have a potential biomarker and therapeutic target for OA. OA cartilage and chondrosarcoma cells were studied to determine the role of miR-29a-3p and PTEN. OA cartilage and human chondrosarcoma cells (SW1353) were obtained. miR-29a-3p and PTEN signature expression was determined by RT-qPCR. The binding relationship between miR-29a-3p and PTEN was investigated by dual-luciferase reporter gene and western blot assay. TUNEL, immunohistochemistry, CCK-8, and flow cytometry were utilized to determine the proliferation and apoptosis of SW1353 cells. This study indicated downregulation of miR-29a-3p expression and upregulation of PTEN expression in human OA primary chondrocytes or OA tissue samples, compared with the normal cartilage cells or tissues. PTEN expression was negatively correlated with miR-29a-3p expression, and miR-29a-3p targeted PTEN mechanistically. miR-29a-3p reduced SW1353 cell activity and proliferation and promoted cell apoptosis. However, the aforementioned effects could be reversed by downregulating PTEN. miR-29a-3p can stimulate chondrocyte proliferation and inhibit apoptosis by inhibiting PTEN expression.

摘要

尽管骨关节炎 (OA) 基因治疗的临床试验取得了重大进展,但 OA 的患病率仍在上升。miRNAs 是 OA 的潜在生物标志物和治疗靶点。研究 OA 软骨和软骨肉瘤细胞,以确定 miR-29a-3p 和 PTEN 的作用。获得 OA 软骨和人软骨肉瘤细胞 (SW1353)。通过 RT-qPCR 确定 miR-29a-3p 和 PTEN 特征表达。通过双荧光素酶报告基因和 Western blot 测定研究 miR-29a-3p 与 PTEN 的结合关系。TUNEL、免疫组织化学、CCK-8 和流式细胞术用于确定 SW1353 细胞的增殖和凋亡。本研究表明,与正常软骨细胞或组织相比,人 OA 原代软骨细胞或 OA 组织样本中 miR-29a-3p 表达下调,PTEN 表达上调。PTEN 表达与 miR-29a-3p 表达呈负相关,miR-29a-3p 通过靶向 PTEN 发挥作用。miR-29a-3p 降低 SW1353 细胞活性和增殖,促进细胞凋亡。然而,下调 PTEN 可以逆转上述作用。miR-29a-3p 通过抑制 PTEN 表达刺激软骨细胞增殖并抑制凋亡。

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本文引用的文献

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Cell Death Discov. 2021 Nov 10;7(1):346. doi: 10.1038/s41420-021-00746-z.
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[ capsule inhibits immune inflammation in osteoarthritis by inhibiting the miR- 23a-3p/PETN/PI3K/AKT/mTOR pathway].[胶囊通过抑制miR-23a-3p/PETN/PI3K/AKT/mTOR通路抑制骨关节炎中的免疫炎症]
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