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病理性近视合并白内障患者晶状体前囊膜中长链非编码RNA的表达

Expression of LncRNAs in anterior capsule of lens in patients with pathologic myopia complicated with cataract.

作者信息

Hu Yaru, Fan Yuchen, Li Na, Xu Che, Wang Jianfeng

机构信息

Department of Ophthalmology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, Anhui, China.

Department of Ophthalmology, Fuyang People's Hospital, Fuyang, 236000, Anhui, China.

出版信息

Int Ophthalmol. 2024 Dec 16;45(1):10. doi: 10.1007/s10792-024-03366-5.

Abstract

PURPOSE

To explore the expressions and functions of lncRNAs in the pathogenesis of pathologic myopia complicated with cataract (PMC).

METHODS

The anterior capsular tissues were collected from patients with age-related cataract (ARC) and PMC. One group of the samples was used to detected by whole-transcriptome sequencing (LC-Bio, Hangzhou, China) and investigated by GO and KEGG enrichment analysis. We selected the Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1), predicted the miRNAs with gene binding sites to it and the downstream mRNAs with gene binding sites to miRNAs through the Starbase and Targetscan websites. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed on the other group to further preliminarily validate the prediction.

RESULTS

A total of 471 lncRNAs were significantly differential expressed in PMC group compared with ARC group, in which 231 lncRNAs were up-regulated, including MALAT1, and 240 lncRNAs were down-regulated. GO and KEGG enrichment analysis showed that lncRNAs targeted differential mRNAs were involved in various biological functions, cell components, molecular functions and signaling pathways. Taking MALAT1 as an example, we predicted that it had binding sites with 113 miRNAs such as hsa-miR-20a-5p, has-miR-20b-5p, hsa-miR-26a-5p, has-miR-106-5p and hsa-miR-204-5p, which were lower in PMC group than these in ARC group. Inversely, the downstream mRNAs of the above miRNAs, such as MMP9, TNF-α, TGF-β2, NF-KB, IL6 and Smad4 were higher.

CONCLUSION

The differentially expressed lncRNAs, especially MALAT1, may act as ceRNA via sponging miRNAs and to regulate the targeting downstream mRNAs in development of PMC and participate in numerous biological processes through interconnected signaling pathways.

摘要

目的

探讨长链非编码RNA(lncRNAs)在病理性近视合并白内障(PMC)发病机制中的表达及作用。

方法

收集年龄相关性白内障(ARC)患者和PMC患者的前囊膜组织。一组样本采用全转录组测序(中国杭州LC-Bio公司)检测,并进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。我们选择了转移相关肺腺癌转录本1(MALAT1),通过Starbase和Targetscan网站预测与其具有基因结合位点的微小RNA(miRNAs)以及与miRNAs具有基因结合位点的下游信使核糖核酸(mRNAs)。另一组样本进行定量实时聚合酶链反应(qRT-PCR)以进一步初步验证预测结果。

结果

与ARC组相比,PMC组共有471个lncRNAs显著差异表达,其中231个lncRNAs上调,包括MALAT1,240个lncRNAs下调。GO和KEGG富集分析表明,lncRNAs靶向的差异mRNAs参与了各种生物学功能、细胞成分、分子功能和信号通路。以MALAT1为例,我们预测它与113个miRNAs如hsa-miR-20a-5p、has-miR-20b-5p、hsa-miR-26a-5p、has-miR-106-5p和hsa-miR-204-5p具有结合位点,这些miRNAs在PMC组中的表达低于ARC组。相反,上述miRNAs的下游mRNAs如基质金属蛋白酶9(MMP9)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β2(TGF-β2)、核因子-κB(NF-KB)、白细胞介素6(IL6)和Smad4则较高。

结论

差异表达的lncRNAs,尤其是MALAT1,可能通过充当竞争性内源RNA(ceRNA)来海绵化miRNAs,并在PMC的发生发展过程中调节靶向的下游mRNAs,通过相互关联的信号通路参与众多生物学过程。

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