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长链非编码 RNA 介导的 ceRNA 网络在骨肉瘤中的调控机制。

The regulatory mechanism of LncRNA-mediated ceRNA network in osteosarcoma.

机构信息

Department of Orthopedics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Department of Orthopedics, The Children's Hospital of Guangxi Zhuang Autonomous Region, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.

出版信息

Sci Rep. 2022 May 24;12(1):8756. doi: 10.1038/s41598-022-11371-w.

DOI:10.1038/s41598-022-11371-w
PMID:35610231
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9130241/
Abstract

Aberrantly expressed lncRNAs have been reported to be closely related to the oncogenesis and development of osteosarcoma. However, the role of a dysregulated lncRNA-miRNA-mRNA network in osteosarcoma in the same individual needs to be further investigated. Whole transcriptome sequencing was performed on the tumour tissues and matched paratumour tissues of three patients with confirmed osteosarcoma. Two divergent lncRNA-miRNA-mRNA regulatory networks were constructed in accordance with their biological significance. The GO and KEGG analysis results of the mRNAs in the two networks revealed that the aberrantly expressed lncRNAs were involved in regulating bone growth and development, epithelial cell proliferation, cell cycle arrest and the N-terminal acetylation of proteins. The survival analysis results of the two networks showed that patients with high expression of GALNT3, FAM91A1, STC2 and SLC7A1 end in poorer prognosis. Likewise, patients with low expression of IGF2, BLCAP, ZBTB47, THRB, PKIA and MITF also had poor prognosis. A subnetwork was then constructed to demonstrate the key genes regulated by aberrantly expressed lncRNAs at the posttranscriptional level via the ceRNA network. Aberrantly expressed lncRNAs in osteosarcoma tissues regulate genes involved in cellular proliferation, differentiation, angiogenesis and the cell cycle via the ceRNA network.

摘要

异常表达的 lncRNAs 与骨肉瘤的发生发展密切相关。然而,同一个体中失调的 lncRNA-miRNA-mRNA 网络在骨肉瘤中的作用仍需进一步研究。对 3 名确诊骨肉瘤患者的肿瘤组织和配对的瘤旁组织进行了全转录组测序。根据其生物学意义构建了两个发散的 lncRNA-miRNA-mRNA 调控网络。这两个网络中 mRNAs 的 GO 和 KEGG 分析结果表明,异常表达的 lncRNAs 参与调节骨的生长和发育、上皮细胞增殖、细胞周期停滞和蛋白质 N 端乙酰化。两个网络的生存分析结果表明,GALNT3、FAM91A1、STC2 和 SLC7A1 表达水平高的患者预后较差。同样,IGF2、BLCAP、ZBTB47、THRB、PKIA 和 MITF 表达水平低的患者预后也较差。然后构建了一个子网络,以通过 ceRNA 网络展示异常表达的 lncRNAs 在转录后水平调节与细胞增殖、分化、血管生成和细胞周期相关的关键基因。骨肉瘤组织中的异常表达的 lncRNAs 通过 ceRNA 网络调节与细胞增殖、分化、血管生成和细胞周期相关的基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9d7/9130241/0d75ba9ae548/41598_2022_11371_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9d7/9130241/6eb52ba00434/41598_2022_11371_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9d7/9130241/c144a9cd52c1/41598_2022_11371_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9d7/9130241/8e8dc643df40/41598_2022_11371_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9d7/9130241/0d75ba9ae548/41598_2022_11371_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9d7/9130241/6eb52ba00434/41598_2022_11371_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9d7/9130241/070be4ce1f34/41598_2022_11371_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9d7/9130241/1e50fdb764f5/41598_2022_11371_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9d7/9130241/bcda50236499/41598_2022_11371_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9d7/9130241/3059bb889e60/41598_2022_11371_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9d7/9130241/c144a9cd52c1/41598_2022_11371_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9d7/9130241/8e8dc643df40/41598_2022_11371_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9d7/9130241/0d75ba9ae548/41598_2022_11371_Fig8_HTML.jpg

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