Prostate adenocarcinoma (PRAD) is the second leading cause of death in men and the key factor that attributes to the severity and higher mortality rates is the tumor's ability to promote osteoblastic metastases (OM). Currently, no blood-based biomarkers are present that bridges the crosstalk between PRAD and OM progression. Conversely, circulatory microRNAs (miRNAs) are gaining interest among the scientific community for its potential as blood-based markers for cancer detection. Using computational pipeline, this study screened exosome-based miRNA that is functionally regulating OM in PRAD. We retrieved the expression profile of miRNA, mRNA from PRAD microarray, and RNA-Seq samples deposited in global repositories and identified the differentially expressed miRNAs (DEMs) and differentially expressed genes. Thereafter, the average expression of the miRNAs was identified in extracellular vesicle specifically in exosomes. Survival analysis and clinical profiling identified functionally significant miR-92a-3p to be a key factor in OM. This was further examined by the interactions with various noncoding RNA elements, transcription factors, oncogenes, tumor suppressor genes, and protein kinases regulated by miR-92a-3p. Identifying the expression pattern, nodal metastasis, Gleason score, and hazard ratio deciphered the critical role of the targets regulated by miR-92a-3p. Further, binding association analyzed through energy, seed match and accessibility showed the miRNA-targets involved in cytokine, TGF-β, and Wnt signaling having close regulatory role in promoting OM. Our findings highlight the potent role of miR-92a-3p as blood-based diagnostic biomarker for OM. The comprehensive insights from our study can be elemental in designing diagnostic biomarker for PRAD.

中文翻译：

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基于循环外泌体的miR-92a-3p对前列腺腺癌成骨细胞转移的诊断作用综合分析

前列腺腺癌（PRAD）是男性第二大死亡原因，其严重性和较高死亡率的关键因素是肿瘤促进成骨细胞转移（OM）的能力。目前，尚不存在能够弥合 PRAD 和 OM 进展之间串扰的血液生物标志物。相反，循环 microRNA (miRNA) 因其作为癌症检测的血液标记物的潜力而引起了科学界的兴趣。本研究利用计算流程筛选了在 PRAD 中功能调节 OM 的基于外泌体的 miRNA。我们检索了保存在全球存储库中的 miRNA、PRAD 微阵列中的 mRNA 和 RNA-Seq 样本的表达谱，并鉴定了差异表达的 miRNA (DEM) 和差异表达的基因。此后，在细胞外囊泡、特别是外泌体中鉴定了 miRNA 的平均表达。生存分析和临床分析确定具有功能意义的 miR-92a-3p 是 OM 的关键因素。通过与 miR-92a-3p 调节的各种非编码 RNA 元件、转录因子、癌基因、肿瘤抑制基因和蛋白激酶的相互作用进一步检查了这一点。识别表达模式、淋巴结转移、格里森评分和风险比破译了 miR-92a-3p 调节靶点的关键作用。此外，通过能量、种子匹配和可及性分析的结合关联表明，参与细胞因子、TGF-β和Wnt信号传导的miRNA靶标在促进OM中具有密切的调节作用。我们的研究结果强调了 miR-92a-3p 作为 OM 血液诊断生物标志物的重要作用。我们研究的全面见解对于设计 PRAD 诊断生物标志物至关重要。