microRNA-1246 Is an Exosomal Biomarker for Aggressive Prostate Cancer.
microRNA-1246 Is an Exosomal Biomarker for Aggressive Prostate Cancer.
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DOI：
10.1158/0008-5472.can-17-2069
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发表时间：
2018-04-01
期刊：
影响因子：
11.2
通讯作者：
Saini S
中科院分区：
文献类型：
--
作者：
Bhagirath D;Yang TL;Bucay N;Sekhon K;Majid S;Shahryari V;Dahiya R;Tanaka Y;Saini S
由于高度异质性，基于活检取样的前列腺癌（PCa）的分子表征通常具有挑战性。因此，确定患者肿瘤的分子印记以进行风险分层的微创方法将是有利的。在这项研究中，我们采用了一种新的，数字扩增的量化方法，使用nCounter技术（Nanostring Technologies）来分析外泌体血清miRNA（ex-miRNA），从积极的PCa病例，良性前列腺增生（BPH），和无病对照。我们鉴定了几种失调的miRNAs，其中之一是肿瘤抑制因子miR-1246。miR-1246在PCa临床组织和细胞系中下调，并选择性地释放到外泌体中。在PCa细胞系中过表达miR-1246可显著抑制体内异种移植肿瘤生长，并增加细胞凋亡，降低体外增殖、侵袭和迁移。miR-1246抑制N-cadherin和vimentin活性，从而抑制上皮-间充质转化。Ex-miR-1246表达与病理分级升高、阳性转移和预后不良相关。我们的分析表明，ex-miR-1246是一种有前途的PCa生物标志物，具有诊断潜力，可以预测疾病的侵袭性。
Due to high heterogeneity, molecular characterization of prostate cancer (PCa) based on biopsy sampling is often challenging. Hence, a minimally invasive method to determine the molecular imprints of a patient's tumor for risk stratification would be advantageous. In this study, we employ a novel, digital amplification-free quantification method using the nCounter technology (Nanostring Technologies) to profile exosomal serum miRNAs (ex-miRNA) from aggressive PCa cases, benign prostatic hyperplasia (BPH), and disease-free controls. We identified several dysregulated miRNAs, one of which was the tumor suppressor miR-1246. miR-1246 was downregulated in PCa clinical tissues and cell lines and was selectively released into exosomes. Overexpression of miR-1246 in a PCa cell line significantly inhibited xenograft tumor growth in vivo and increased apoptosis and decreased proliferation, invasiveness, and migration in vitro. miR-1246 inhibited N-cadherin and vimentin activities, thereby inhibiting epithelial-mesenchymal transition. Ex-miR-1246 expression correlated with increasing pathological grade, positive metastasis, and poor prognosis. Our analyses suggest ex-miR-1246 as a promising PCa biomarker with diagnostic potential that can predict disease aggressiveness.