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解码良性前列腺增生中的ceRNA调控网络和自噬相关基因。

Decoding ceRNA regulatory network and autophagy-related genes in benign prostatic hyperplasia.

作者信息

Zhou Liang, Li Youyou, Li Jiaren, Yao Hanyu, Huang Jin, Li Cheng, Wang Long

机构信息

Department of Urology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.

Department of Urology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.

出版信息

Int J Biol Macromol. 2023 Jan 15;225:997-1009. doi: 10.1016/j.ijbiomac.2022.11.162. Epub 2022 Nov 17.

Abstract

Benign prostatic hyperplasia (BPH) is a common disease among aging males. We obtained BPH transcriptional signatures by high-throughput RNA sequencing analysis. Accordingly, we determined the differentially expressed RNAs (DERNAs) between BPH tissues and normal prostate tissues. WebGestalt and R package (clusterprofiler) was used to enrichment analysis. Clinical correlations were analyzed using Spearman's coefficient. TargetScan, ENCORI, miRNet, and miRDB databases were used to predict targets' relationships in ceRNA networks. Immunofluorescence staining and qRT-PCR analyses were performed to validate the findings. Microarray analysis of the datasets showed 369 DElncRNAs, 122 DEpseudogenes, 6 DEmiRNAs and 1358 DEmRNAs. DEmRNAs were particularly enriched in the autophagy-related pathways. Following the screening of DEmRNAs and autophagy-related genes (ARGs), 50 DEARGs were selected. MCODE analysis on Cytoscape was performed for the 50 DEARGs, and 3 hub genes (ATF4, XBP1, and PPP1R15A) were obtained. Spearman's correlation analysis showed that the mRNA expression of XBP1 correlated positively with age, total score, and storage score, but negatively with the maximum flow rate. Subsequently, the pseudogene/lncRNA- hsa-miR-222-3p-XBP1 pathway was identified. Our findings elucidate that the pseudogene/lncRNA-hsa-miR-222-3p-XBP1 pathway may play a regulatory role in the occurrence of BPH through autophagy.

摘要

良性前列腺增生(BPH)是老年男性中的常见疾病。我们通过高通量RNA测序分析获得了BPH转录特征。据此,我们确定了BPH组织与正常前列腺组织之间的差异表达RNA(DERNA)。使用WebGestalt和R包(clusterprofiler)进行富集分析。使用Spearman系数分析临床相关性。使用TargetScan、ENCORI、miRNet和miRDB数据库预测ceRNA网络中的靶标关系。进行免疫荧光染色和qRT-PCR分析以验证研究结果。数据集的微阵列分析显示369个差异表达的长链非编码RNA(DElncRNA)、122个差异表达的假基因、6个差异表达的微小RNA(DEmiRNA)和1358个差异表达的信使RNA(DEmRNA)。DEmRNA特别富集于自噬相关途径。在筛选DEmRNA和自噬相关基因(ARG)后,选择了50个差异表达自噬相关基因(DEARG)。对这50个DEARG在Cytoscape上进行MCODE分析,获得了3个枢纽基因(ATF4、XBP1和PPP1R15A)。Spearman相关性分析表明,XBP1的mRNA表达与年龄、总分和储尿期评分呈正相关,但与最大尿流率呈负相关。随后,鉴定出假基因/长链非编码RNA-hsa-miR-222-3p-XBP1途径。我们的研究结果表明,假基因/长链非编码RNA-hsa-miR-222-3p-XBP1途径可能通过自噬在BPH的发生中发挥调节作用。

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