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分析 PANoptosis 相关 ceRNA 网络揭示长非编码 RNA MIR17HG 参与肿瘤坏死因子-α抑制成骨分化。

Analysis of PANoptosis-related ceRNA network reveals lncRNA MIR17HG involved in osteogenic differentiation inhibition impaired by tumor necrosis factor-α.

机构信息

The Affiliated Guangdong Second Provincial General Hospital of Jinan University, No. 466 Xingang Road, Haizhu District, Guangzhou, 510317, Guangdong, People's Republic of China.

Department of Orthopaedics, Southern Medical University, Guangzhou, Guangdong, China.

出版信息

Mol Biol Rep. 2024 Aug 15;51(1):909. doi: 10.1007/s11033-024-09810-0.

DOI:10.1007/s11033-024-09810-0
PMID:39145884
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11327206/
Abstract

BACKGROUND

Inflammatory cytokines such as Interleukin 1β(IL1β), IL6,Tumor Necrosis Factor-α (TNF-α) can inhibit osteoblast differentiation and induce osteoblast apoptosis. PANoptosis, a newly identified type of programmed cell death (PCD), may be influenced by long noncoding RNA (lncRNAs) which play important roles in regulating inflammation. However, the potential role of lncRNAs in inflammation and PANoptosis during osteogenic differentiation remains unclear. This study aimed to investigate the regulatory functions of lncRNAs in inflammation and apoptosis during osteogenic differentiation.

METHODS AND RESULTS

High-throughput sequencing was used to identify differentially expressed genes involved in osteoblast differentiation under inflammatory conditions. Two lncRNAs associated with inflammation and PANoptosis during osteogenic differentiation were identified from sequencing data and Gene Expression Omnibus (GEO) databases. Their functionalities were analyzed using diverse bioinformatics methodologies, resulting in the construction of the lncRNA-miRNA-mRNA network. Among these, lncRNA (MIR17HG) showed a high correlation with PANoptosis. Bibliometric methods were employed to collect literature data on PANoptosis, and its components were inferred. PCR and Western Blotting experiments confirmed that lncRNA MIR17HG is related to PANoptosis in osteoblasts during inflammation.

CONCLUSIONS

Our data suggest that TNF-α-induced inhibition of osteogenic differentiation and PANoptosis in MC3T3-E1 osteoblasts is associated with MIR17HG. These findings highlight the critical role of MIR17HG in the interplay between inflammation, PANoptosis, and osteogenic differentiation, suggesting potential therapeutic targets for conditions involving impaired bone formation and inflammatory responses.

摘要

背景

白细胞介素 1β(IL1β)、IL6、肿瘤坏死因子-α(TNF-α)等炎症细胞因子可抑制成骨细胞分化并诱导成骨细胞凋亡。PANoptosis 是一种新发现的程序性细胞死亡(PCD)类型,可能受到长链非编码 RNA(lncRNAs)的影响,lncRNAs 在调节炎症中发挥重要作用。然而,lncRNAs 在成骨分化过程中的炎症和 PANoptosis 中的潜在作用尚不清楚。本研究旨在探讨 lncRNAs 在成骨分化过程中炎症和细胞凋亡中的调节作用。

方法和结果

高通量测序用于鉴定炎症条件下成骨分化过程中涉及的差异表达基因。从测序数据和基因表达综合数据库中确定了与成骨分化过程中的炎症和 PANoptosis 相关的两个 lncRNAs。使用多种生物信息学方法分析它们的功能,构建 lncRNA-miRNA-mRNA 网络。其中,lncRNA(MIR17HG)与 PANoptosis 高度相关。文献计量学方法用于收集关于 PANoptosis 的文献数据,并推断其组成。PCR 和 Western Blotting 实验证实,lncRNA MIR17HG 与炎症期间成骨细胞中的 PANoptosis 相关。

结论

我们的数据表明,TNF-α诱导的 MC3T3-E1 成骨细胞成骨分化抑制和 PANoptosis 与 MIR17HG 有关。这些发现强调了 MIR17HG 在炎症、PANoptosis 和成骨分化之间相互作用中的关键作用,为涉及骨形成受损和炎症反应的疾病提供了潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03a4/11327206/f5330434fcb1/11033_2024_9810_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03a4/11327206/908f53835441/11033_2024_9810_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03a4/11327206/43d299b0adb1/11033_2024_9810_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03a4/11327206/4248809f3d01/11033_2024_9810_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03a4/11327206/d15b9330cc2d/11033_2024_9810_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03a4/11327206/3b4a39cce09f/11033_2024_9810_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03a4/11327206/af016edf1e44/11033_2024_9810_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03a4/11327206/f5330434fcb1/11033_2024_9810_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03a4/11327206/908f53835441/11033_2024_9810_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03a4/11327206/64fe4e2424e7/11033_2024_9810_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03a4/11327206/b0cae79558fc/11033_2024_9810_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03a4/11327206/43d299b0adb1/11033_2024_9810_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03a4/11327206/4248809f3d01/11033_2024_9810_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03a4/11327206/d15b9330cc2d/11033_2024_9810_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03a4/11327206/3b4a39cce09f/11033_2024_9810_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03a4/11327206/af016edf1e44/11033_2024_9810_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03a4/11327206/f5330434fcb1/11033_2024_9810_Fig9_HTML.jpg

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