外泌体衍生的微小RNA作为前列腺骨转移的潜在生物标志物
Exosome-Derived miRNAs as Potential Biomarkers for Prostate Bone Metastasis.
作者信息
Lu Zhenquan, Hou Jian, Li Xiao, Zhou Jun, Luo Bingfeng, Liang Songwu, Lo Richard K, Wong Tak Man, Kuang Guan-Ming
机构信息
Department of Urology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People's Republic of China.
Department of Orthopaedics and Traumatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People's Republic of China.
出版信息
Int J Gen Med. 2022 Jun 1;15:5369-5383. doi: 10.2147/IJGM.S361981. eCollection 2022.
PURPOSE
The purpose of this study was to identify the potential exosome-derived microRNAs (miRNAs) related to prostate cancer (Pca) bone metastasis.
METHODS
Two datasets were collected. One dataset was from the authors' institute, for which two groups of 10 patients each were designed: in the first one, the patients had early-stage localised Pca without bone metastasis, and in the other, the patients presented with Pca with bone metastasis. Then, the miRNA expression profiles of the blood exosomes were obtained and analysed. The other dataset was a public dataset of the miRNA expression transcriptome (GSE26964), which was downloaded from Gene Expression Omnibus (GEO). The results of both datasets were jointly analysed and the most bone-metastatic-related differentially expressed miRNAs (diff-miRNAs) were identified and further validated. Finally, a series of bioinformatics analyses were performed and the relationship between target genes of the diff-miRNAs and the pathogenesis and progression of bone metastasis of Pca were studied.
RESULTS
From the authors' dataset, in all, 313 diff-miRNAs were identified, of which 205 were up-regulated while 108 were down-regulated. From the GSE26964 dataset, 107 diff-miRNAs were found, of which 44 were up-regulated and 63 were down-regulated. Taking the intersection of the results of both datasets, four diff-miRNAs were identified: hsa-miR-125a-3p, hsa-miR-330-3p, hsa-miR-339-5p and hsa-miR-613. In all, 94 target genes of the four diff-miRNAs were predicted. After considering the intersection of the results from the GSE32269 dataset, we obtained 25 target genes. Although either positive or negative correlations were found among the diff-miRNAs with some of the target genes, there is a lack of evidence on how such correlations regulate the development and promotion of Pca bone metastasis.
CONCLUSION
Hsa-miR-125a-3p, hsa-miR-330-3p, hsa-miR-339-5p and hsa-miR-613 are potential biomarkers for Pca bone metastasis.
目的
本研究旨在鉴定与前列腺癌（Pca）骨转移相关的潜在外泌体衍生微小RNA（miRNA）。
方法
收集了两个数据集。一个数据集来自作者所在机构，设计了两组，每组10例患者：第一组患者患有无骨转移的早期局限性Pca，另一组患者患有伴有骨转移的Pca。然后，获取并分析血液外泌体的miRNA表达谱。另一个数据集是miRNA表达转录组的公共数据集（GSE26964），从基因表达综合数据库（GEO）下载。对两个数据集的结果进行联合分析，鉴定出与骨转移最相关的差异表达miRNA（差异miRNA）并进一步验证。最后，进行了一系列生物信息学分析，研究了差异miRNA的靶基因与Pca骨转移的发病机制及进展之间的关系。
结果
从作者的数据集中，共鉴定出313个差异miRNA，其中205个上调，108个下调。从GSE26964数据集中，发现了107个差异miRNA，其中44个上调，63个下调。取两个数据集结果的交集，鉴定出4个差异miRNA：hsa-miR-125a-3p、hsa-miR-330-3p hsa-miR-339-5p和hsa-miR-613。共预测了这4个差异miRNA的94个靶基因。考虑GSE32269数据集结果的交集后，我们得到了25个靶基因。尽管在差异miRNA与一些靶基因之间发现了正相关或负相关，但缺乏关于这种相关性如何调节Pca骨转移的发生和发展的证据。
结论
Hsa-miR-125a-3p、hsa-miR-330-3p、hsa-miR-339-5p和hsa-miR-613是Pca骨转移的潜在生物标志物。
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