探索肥大韧带患者的 lncRNA 表达模式

IF 3.8 2区 医学 Q1 CLINICAL NEUROLOGY Neurospine Pub Date : 2024-03-01 Epub Date: 2024-01-29 DOI:10.14245/ns.2346994.497
Junling Chen, Guibin Zhong, Manle Qiu, Wei Ke, Jingsong Xue, Jianwei Chen
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引用次数: 0

摘要

背景:黄韧带肥厚症(LFH)是腰椎管狭窄症的常见病因,可导致严重的残疾和发病率。尽管长非编码 RNA(lncRNA)与多种生物过程和疾病有关,但它们在腰椎黄韧带肥大症中的参与仍未得到充分了解。方法:使用 lncRNA 测序分析人类黄韧带样本,然后通过定量实时聚合酶链反应进行验证。为了探索不同表达的lncRNA相关基因的潜在生物学功能,我们进行了基因本体(GO)和京都基因组百科全书(KEGG)通路分析。我们还研究了lncRNA PARD3-AS1对LFH体外进展的影响:结果:与非肥厚性黄韧带(LFN)组织相比,LFH组织中共有1091个lncRNA表现出差异表达,其中645个上调,446个下调。根据GO分析,差异表达的转录本主要参与代谢过程、细胞器、核腔、细胞质、蛋白质结合、核酸结合和转录因子活性。此外,KEGG通路分析表明,差异表达的lncRNA与hippo信号通路、核苷酸切除修复和核因子-kappa B信号通路有关。PARD3-AS1、RP11-430G17.3、RP1-193H18.3和H19的表达与测序分析结果一致。抑制 PARD3-AS1 可抑制 LFH 细胞的纤维化,而过表达 PARD3-AS1 则可促进体外 LFH 细胞的纤维化:本研究发现了与LFH相关的lncRNAs的不同表达模式,为了解LFH的内在机制以及潜在的预后和治疗干预提供了见解。值得注意的是,PARD3-AS1 似乎在 LFH 的病理生理学中发挥了重要作用。
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Exploring lncRNA Expression Patterns in Patients With Hypertrophied Ligamentum Flavum.

Objective: Hypertrophy ligamentum flavum (LFH) is a common cause of lumbar spinal stenosis, resulting in significant disability and morbidity. Although long noncoding RNAs (lncRNAs) have been associated with various biological processes and disorders, their involvement in LFH remains not fully understood.

Methods: Human ligamentum flavum samples were analyzed using lncRNA sequencing followed by validation through quantitative real-time polymerase chain reaction. To explore the potential biological functions of differentially expressed lncRNA-associated genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. We also studied the impact of lncRNA PARD3-AS1 on the progression of LFH in vitro.

Results: In the LFH tissues when compared to that in the nonhypertrophic ligamentum flavum (LFN) tissues, a total of 1,091 lncRNAs exhibited differential expression, with 645 upregulated and 446 downregulated. Based on GO analysis, the differentially expressed transcripts primarily participated in metabolic processes, organelles, nuclear lumen, cytoplasm, protein binding, nucleic acid binding, and transcription factor activity. Moreover, KEGG pathway analysis indicated that the differentially expressed lncRNAs were associated with the hippo signaling pathway, nucleotide excision repair, and nuclear factor-kappa B signaling pathway. The expression of PARD3-AS1, RP11-430G17.3, RP1-193H18.3, and H19 was confirmed to be consistent with the sequencing analysis. Inhibition of PARD3-AS1 resulted in the suppression of fibrosis in LFH cells, whereas the overexpression of PARD3-AS1 promoted fibrosis in LFH cells in vitro.

Conclusion: This study identified distinct expression patterns of lncRNAs that are linked to LFH, providing insights into its underlying mechanisms and potential prognostic and therapeutic interventions. Notably, PARD3-AS1 appears to play a significant role in the pathophysiology of LFH.

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来源期刊
Neurospine
Neurospine Multiple-
CiteScore
5.80
自引率
18.80%
发文量
93
审稿时长
10 weeks
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