Effect Of XBP1 Deficiency In Cartilage On The Regulatory Network Of LncRNA/circRNA-miRNA-mRNA.

Effect Of XBP1 Deficiency In Cartilage On The Regulatory Network Of LncRNA/circRNA-miRNA-mRNA.
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软骨中 XBP1 缺陷对 LncRNA/circRNA-miRNA mRNA 调节网络的影响。

DOI:
10.7150/ijbs.64054
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发表时间:
2022
影响因子:
9.2
通讯作者:
Guo F
Guo F
中科院分区:
生物学2区
文献类型:
--
作者:
Li X;Yang Y;Liang L;Fan M;Li X;Feng N;Pan Y;Tan Q;Xu Q;Xie Y;Guo F

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X-box结合蛋白1(X-box binding protein 1,XBP 1)是内质网应激中未折叠蛋白反应(unfolded protein response,UPR)的重要组成部分。根据先前对不同的XBP 1缺陷小鼠进行的研究,XBP 1基因影响小鼠软骨发育并导致其他相关疾病。然而,当软骨细胞中缺乏XBP 1时,包括mRNA和ncRNA在内的完整转录组如何影响软骨和其他组织的功能尚不清楚。本研究旨在利用高通量测序技术筛选XBP 1软骨特异性基因敲除(CKO)小鼠差异表达的mRNA、circRNA、lncRNA和miRNA,构建circRNA-miRNA-mRNA和lncRNA-miRNA-mRNA调控网络。鉴定了XBP 1 CKO小鼠和对照组软骨组织之间的DE LncRNA(DE-LncRNA)、circRNA(DE-circRNA)、miRNA(DE-miRNA)和mRNA [差异表达基因(DEG)],包括441个DE-LncRNA、15个DE-circRNA、6个DE-miRNA和477个DEG。此外,基于lncRNA/circRNA、miRNA、mRNA之间的相关性,构建了253,235个lncRNA-miRNA-mRNA网络和1,822个circRNA-miRNA-mRNA网络。全转录组分析表明,软骨中的XBP 1缺陷会影响软骨和其他不同组织的功能,以及相关疾病。总的来说,我们的研究结果可能为软骨和其他相关疾病的诊断和治疗提供潜在的生物标志物和机制。
X-box binding protein 1(XBP1) is a critical component for unfolded protein response (UPR) in ER stress. According to previous studies performed with different XBP1-deficient mice, the XBP1 gene affects mouse cartilage development and causes other related diseases. However, how the complete transcriptome, including mRNA and ncRNAs, affects the function of cartilage and other tissues when XBP1 is deficient in chondrocytes is unclear. In this study, we aimed to screen the differentially expressed (DE) mRNAs, circRNAs, lncRNAs and miRNAs in XBP1 cartilage-specific knockout (CKO) mice using high throughput sequencing and construct the circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA regulatory networks. DE LncRNAs (DE-LncRNAs), circRNAs (DE-circRNAs), miRNAs (DE-miRNAs), and mRNAs [differentially expressed genes (DEGs)] between the cartilage tissue of XBP1 CKO mice and controls were identified, including 441 DE-LncRNAs, 15 DE-circRNAs, 6 DE-miRNAs, and 477 DEGs. Further, 253,235 lncRNA-miRNA-mRNA networks and 1,822 circRNA-miRNA-mRNA networks were constructed based on the correlation between lncRNAs/circRNAs, miRNAs, mRNAs. The whole transcriptome analysis revealed that XBP1 deficiency in cartilage affects the function of cartilage and other different tissues, as well as associated diseases. Overall, our findings may provide potential biomarkers and mechanisms for the diagnosis and treatment of cartilage and other related diseases.
通过整合大规模 CLIP-Seq 和 RNA-Seq 数据集发现蛋白质-lncRNA 相互作用。
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