Laboratory of Genetic Medicine and Immunology, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar.
Department of Urology, Hamad Medical Corporation, Doha, Qatar.
J Transl Med. 2017 Dec 21;15(1):260. doi: 10.1186/s12967-017-1362-x.
Prostate cancer (PCa) is a complex disorder resulting from the combined effects of multiple environmental and genetic factors. Small non-coding RNAs (sRNAs), particularly microRNAs (miRNAs), regulate several cellular processes and have an important role in many human malignancies including PCa. We assessed the sRNA profiles associated with PCa in Arabs, a population that has rarely been studied.
We used next generation sequencing technology to obtain the entire sRNA transcriptome of primary prostate tumor formalin-fixed paraffin-embedded tissues, and their paired non-tumor tissues, collected from Bedouin patients (Qatari and Saudi). The miRNA and the target gene expression were evaluated by real-time quantitative PCR. miRNA KEGG pathway and miRNA target genes were subsequently analyzed by starBase and TargetScan software.
Different expression patterns of several sRNA and miRNA editing were revealed between PCa tumor and their paired non-tumor tissues. Our study identified four miRNAs that are strongly associated with prostate cancer, which have not been reported previously. Differentially expressed miRNAs significantly affect various biological pathways, such as cell cycle, endocytosis, adherence junction and pathways involved in cancer. Prediction of potential targets for the identified miRNAs indicates the overexpression of KRAS, BCL2 and down-regulation of PTEN in PCa tumor tissues.
These miRNAs, newly associated with prostate cancer, may represent not only markers for the increased risk of PCa in Arabs, but may also reflect the clinical and pathological diversity as well as the ethno-specific heterogeneity of prostate cancer.
前列腺癌（PCa）是一种复杂的疾病，是多种环境和遗传因素共同作用的结果。小非编码 RNA（sRNAs），特别是 microRNAs（miRNAs），调节着多种细胞过程，在包括 PCa 在内的许多人类恶性肿瘤中发挥着重要作用。我们评估了阿拉伯人群中与 PCa 相关的 sRNA 谱，阿拉伯人群很少被研究。
我们使用下一代测序技术获得了来自贝都因患者（卡塔尔和沙特）的原发性前列腺肿瘤福尔马林固定石蜡包埋组织及其配对非肿瘤组织的全 sRNA 转录组。通过实时定量 PCR 评估 miRNA 和靶基因的表达。随后使用 starBase 和 TargetScan 软件分析 miRNA KEGG 途径和 miRNA 靶基因。
揭示了 PCa 肿瘤与其配对非肿瘤组织之间几种 sRNA 和 miRNA 编辑的不同表达模式。我们的研究确定了四个与前列腺癌强烈相关的 miRNA，这些 miRNA 以前尚未报道过。差异表达的 miRNA 显著影响各种生物学途径，如细胞周期、内吞作用、粘附连接和癌症相关途径。对鉴定出的 miRNA 的潜在靶基因的预测表明，KRAS、BCL2 的过表达和 PTEN 的下调与 PCa 肿瘤组织有关。
这些新与前列腺癌相关的 miRNA，不仅可能代表阿拉伯人 PCa 风险增加的标志物，而且可能反映前列腺癌的临床和病理多样性以及种族特异性异质性。
