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长链非编码RNA通过全局调控mRNA和miRNA表达来调节人脐静脉内皮细胞的细胞功能。

LncRNA Regulates the Cellular Function of HUVECs by Globally Regulating mRNA and miRNA Expression.

作者信息

Gong Zhiqiang, Yang Jin, Dong Junjie, Li Haotian, Wang Bing, Du Kaili, Zhang Chunqiang, Chen Lingqiang

机构信息

Department of Orthopaedics, The First Affiliated Hospital of Kunming Medical University, 650032 Kunming, Yunnan, China.

出版信息

Front Biosci (Landmark Ed). 2022 Dec 21;27(12):330. doi: 10.31083/j.fbl2712330.

Abstract

BACKGROUND

Long non-coding RNA (lncRNA) hypoxia inducible factor 1α-antisense RNA 1 () serves critical roles in cardiovascular diseases (CVDs). Vascular endothelial cells (VECs) are vulnerable to stimuli. Our previous study revealed that knockdown of reduces palmitic acid-induced apoptosis and promotes the proliferation of human VECs (HUVECs); however, the underlying mechanism remains unclear.

MATERIAL AND METHODS

Cell Counting Kit-8, flow cytometry, transwell invasion, and wound healing were applied to detect the function of HUVECs. Moreover, miRNA sequencing (miRNA-seq) and RNA sequencing (RNA-seq) were conducted to uncover its underlying mechanism. Quantitative Polymerase Chain Reaction (qPCR) was implemented to assess the accuracy of miRNA-seq. A co-expression network was generated to determine the relationship between differentially expressed miRNAs (DEmiRNAs) and differentially expressed genes (DEGs).

RESULTS

Knockdown of promoted the proliferation, migration, and invasion but reduced the apoptosis of HUVECs, and the overexpression of this lncRNA had the opposite effect. Numerous DEmiRNAs and DEGs were identified, which might contribute to this phenomenon. Multiple target genes of DEmiRNAs were associated with cell proliferation and apoptosis, and overlapped with DEGs identified from RNA-seq. Finally, the network manifested that lncRNA moderated the function of HUVECs by not only regulating the expression of some genes directly but also by influencing a few miRNAs to indirectly mediate the expression of mRNAs.

CONCLUSIONS

The results suggested that might regulate HUVEC function by not only regulating the expression of some genes directly but also by influencing some miRNAs to indirectly mediate the expression level of mRNA.

摘要

背景

长链非编码RNA(lncRNA)缺氧诱导因子1α反义RNA 1()在心血管疾病(CVD)中发挥关键作用。血管内皮细胞(VEC)易受刺激。我们之前的研究表明,敲低可减少棕榈酸诱导的细胞凋亡并促进人血管内皮细胞(HUVEC)的增殖;然而,其潜在机制仍不清楚。

材料与方法

应用细胞计数试剂盒-8、流式细胞术、Transwell侵袭实验和伤口愈合实验检测HUVEC的功能。此外,进行了miRNA测序(miRNA-seq)和RNA测序(RNA-seq)以揭示其潜在机制。实施定量聚合酶链反应(qPCR)以评估miRNA-seq的准确性。生成共表达网络以确定差异表达的miRNA(DEmiRNA)与差异表达基因(DEG)之间的关系。

结果

敲低促进了HUVEC的增殖、迁移和侵袭,但减少了其凋亡,而这种lncRNA的过表达则产生相反的效果。鉴定出许多DEmiRNA和DEG,这可能导致了这种现象。DEmiRNA的多个靶基因与细胞增殖和凋亡相关,并与从RNA-seq中鉴定出的DEG重叠。最后,该网络表明lncRNA不仅通过直接调节一些基因的表达,还通过影响一些miRNA间接介导mRNA的表达来调节HUVEC的功能。

结论

结果表明,不仅可以通过直接调节一些基因的表达,还可以通过影响一些miRNA间接介导mRNA的表达水平来调节HUVEC的功能。

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