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hsa-miR-199b-3p 通过靶向 CCDC88A 抑制上皮间质转化和 Wnt/β-catenin 信号通路抑制骨肉瘤进展。

hsa-miR-199b-3p suppresses osteosarcoma progression by targeting CCDC88A, inhibiting epithelial-to-mesenchymal transition, and Wnt/beta-catenin signaling pathway.

机构信息

Department of Pediatric Surgery, The First People's Hospital of Lianyungang, 182 Tongguan North Road, Lianyungang, 222000, Jiangsu, People's Republic of China.

Department of Emergency Surgery, The Second People's Hospital of Lianyungang, 41 Hailian East Road, Lianyungang, 222000, Jiangsu, People's Republic of China.

出版信息

Sci Rep. 2023 Aug 2;13(1):12544. doi: 10.1038/s41598-023-39537-0.

DOI:10.1038/s41598-023-39537-0
PMID:37532779
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10397339/
Abstract

The present study investigated microRNA (miR)-199b-3p expression in osteosarcoma (OS) and aimed to identify its potential mechanism of action contributing to the development of this disease. Firstly, miR-199b-3p and coiled-coil domain containing 88A (CCDC88A) expression data were evaluated from Gene Expression Profiling Interactive Analysis and Kaplan Meier plotter was used to assess the survival data. By analyzing the GSE65071 dataset from gene expression omnibus, it was found that miR-199b-3p was expressed at a low level. By using reverse transcription-quantitative PCR analysis in OS cells and tissues, CCDC88A was found to be expressed at a high level. Moreover, TargetScan predicted CCDC88A to be a downstream target of miR-199b-3p. Luciferase reporter assays were used to verify this prediction. In vitro overexpression of miR-199b-3p decreased the invasive and proliferative activity of OS cells. Mechanistic studies indicated that decreased miR-199b-3p resulted in increased expression of CCDC88A. Concomitantly, it impeded the Wnt/beta-catenin pathway and the epithelial-to-mesenchymal transition process. Overall, the results of the present study emphasized the pivotal role of the miR-199b-3p in the formation and progression of OS, suggesting that it could be used as a potential tumor biomarker.

摘要

本研究调查了骨肉瘤(OS)中 microRNA(miR)-199b-3p 的表达,并旨在确定其潜在的作用机制,以促进该疾病的发展。首先,从基因表达谱交互分析中评估了 miR-199b-3p 和卷曲螺旋结构域包含 88A(CCDC88A)的表达数据,并使用 Kaplan-Meier 绘图仪评估了生存数据。通过分析基因表达综合数据库中的 GSE65071 数据集,发现 miR-199b-3p 的表达水平较低。通过对 OS 细胞和组织的逆转录定量 PCR 分析,发现 CCDC88A 的表达水平较高。此外,TargetScan 预测 CCDC88A 是 miR-199b-3p 的下游靶基因。荧光素酶报告基因实验验证了这一预测。体外过表达 miR-199b-3p 降低了 OS 细胞的侵袭和增殖活性。机制研究表明,miR-199b-3p 的表达下调导致 CCDC88A 的表达增加。同时,它抑制了 Wnt/β-catenin 通路和上皮间质转化过程。总的来说,本研究的结果强调了 miR-199b-3p 在 OS 形成和进展中的关键作用,表明它可以作为一种潜在的肿瘤标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45d/10397339/0cc6a5d14931/41598_2023_39537_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45d/10397339/bf92b98cc7ee/41598_2023_39537_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45d/10397339/6913e162f7ac/41598_2023_39537_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45d/10397339/5903cd773670/41598_2023_39537_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45d/10397339/bc6a29fe146b/41598_2023_39537_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45d/10397339/0cc6a5d14931/41598_2023_39537_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45d/10397339/bf92b98cc7ee/41598_2023_39537_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45d/10397339/6913e162f7ac/41598_2023_39537_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45d/10397339/5903cd773670/41598_2023_39537_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45d/10397339/bc6a29fe146b/41598_2023_39537_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45d/10397339/0cc6a5d14931/41598_2023_39537_Fig5_HTML.jpg

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