Schitcu Vlad Horia, Raduly Lajos, Nutu Andreea, Zanoaga Oana, Ciocan Cristina, Munteanu Vlad Cristian, Cojocneanu Roxana, Petrut Bogdan, Coman Ioan, Braicu Cornelia, Berindan-Neagoe Ioana
Research Center for Functional Genomics, Biomedicine, and Translational Medicine, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj-Napoca, 400337, Romania.
Department of Urology, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, 400012, Romania.
Pharmgenomics Pers Med. 2022 Mar 10;15:177-193. doi: 10.2147/PGPM.S348565. eCollection 2022.
Prostate cancer biology is complex, and needs to be deciphered. The latest evidence reveals the significant role of non-coding RNAs, particularly microRNAs (miRNAs), as key regulatory factors in cancer. Therefore, the identification of altered miRNA patterns involved in prostate cancer will allow them to be used for development of novel diagnostic and prognostic biomarkers.
We performed a miRNAs transcriptomic analysis, using microarray (10 matched pairs tumor tissue versus normal adjacent tissue, selected based on inclusion criteria), followed by overlapping with TCGA data. A total of 292 miRNAs were differentially expressed, with 125 upregulated and 167 downregulated in TCGA patients' cohort with PRAD (prostate adenocarcinoma), respectively for the microarray experiments; 16 upregulated and 44 downregulated miRNAs were found in our cohort. To confirm our results obtained for tumor tissue, we performed validation with qRT-PCR at the tissue and plasma level of two selected transcripts, and finally, we focused on the identification of altered miRNAs involved in key biological processes.
A common signature identified a panel of 12 upregulated and 1 downregulated miRNA, targeting and interconnected in a network with the TP53, AGO2, BIRC5 gene and EGFR as a core element. Among this signature, the overexpressed transcripts (miR-20b-5p, miR-96-5p, miR-183-5p) and the downregulated miR-542-5p were validated by qRT-PCR in an additional patients' cohort of 34 matched tumor and normal adjacent paired samples. Further, we performed the validation of the expression level for miR-20b-5p, miR-96-5p, miR-183-5p plasma, on the same patients' cohort versus a healthy control group, confirming the overexpression of these transcripts in the PRAD group, demonstrating the liquid biopsy as a potential investigational tool in prostate cancer.
In this pilot study, we provide evidence on miRNA dysregulation and its association with key functional components of the PRAD landscape, where an important role is acted by miR-20b-5p, miR-542-5p, or the oncogenic cluster miR-183-96-182.
前列腺癌生物学特性复杂，需要深入解析。最新证据表明非编码RNA，尤其是微小RNA（miRNA）在癌症中作为关键调控因子发挥着重要作用。因此，鉴定前列腺癌中miRNA模式的改变将有助于将其用于开发新型诊断和预后生物标志物。
我们进行了miRNA转录组分析，使用微阵列（根据纳入标准选择10对匹配的肿瘤组织与相邻正常组织），随后与TCGA数据进行比对。在TCGA前列腺腺癌（PRAD）患者队列中，总共292种miRNA表达存在差异，在微阵列实验中分别有125种上调和167种下调；在我们的队列中发现16种上调和44种下调的miRNA。为了证实我们在肿瘤组织中获得的结果，我们在两个选定转录本的组织和血浆水平上进行了qRT-PCR验证，最后，我们专注于鉴定参与关键生物学过程的miRNA改变。
一个共同特征鉴定出一组12种上调和1种下调的miRNA，它们以TP53、AGO2、BIRC5基因和EGFR作为核心元件在一个网络中靶向并相互连接。在这个特征中，qRT-PCR在另外34对匹配的肿瘤和相邻正常配对样本的患者队列中验证了过表达的转录本（miR-20b-5p、miR-96-5p、miR-183-5p）和下调的miR-542-5p。此外，我们在同一患者队列与健康对照组中对miR-20b-5p、miR-96-5p、miR-183-5p血浆中的表达水平进行了验证，证实了这些转录本在PRAD组中的过表达，证明液体活检作为前列腺癌潜在研究工具的可行性。
在这项初步研究中，我们提供了miRNA失调及其与PRAD格局关键功能成分关联的证据，其中miR-20b-5p、miR-542-5p或致癌簇miR-183-96-182发挥了重要作用。
