Laios Alexandros, O'Toole Sharon, Flavin Richard, Martin Cara, Kelly Lynn, Ring Martina, Finn Stephen P, Barrett Ciara, Loda Massimo, Gleeson Noreen, D'Arcy Tom, McGuinness Eamonn, Sheils Orla, Sheppard Brian, O' Leary John
Department of Obstetrics and Gynaecology, Trinity College Dublin, Trinity Centre for Health Sciences, St, James's Hospital, Dublin 8, Ireland.
Mol Cancer. 2008 Apr 28;7:35. doi: 10.1186/1476-4598-7-35.
MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression by binding to target mRNAs. miRNAs have not been comprehensively studied in recurrent ovarian cancer, yet an incurable disease.
Using real-time RT-PCR, we obtained distinct miRNA expression profiles between primary and recurrent serous papillary ovarian adenocarcinomas (n = 6) in a subset of samples previously used in a transcriptome approach. Expression levels of top dysregulated miRNA genes, miR-223 and miR-9, were examined using TaqMan PCR in independent cohorts of fresh frozen (n = 18) and FFPE serous ovarian tumours (n = 22). Concordance was observed on TaqMan analysis for miR-223 and miR-9 between the training cohort and the independent test cohorts. Target prediction analysis for the above miRNA "recurrent metastatic signature" identified genes previously validated in our transcriptome study. Common biological pathways well characterised in ovarian cancer were shared by miR-9 and miR-223 lists of predicted target genes. We provide strong evidence that miR-9 acts as a putative tumour suppressor gene in recurrent ovarian cancer. Components of the miRNA processing machinery, such as Dicer and Drosha are not responsible for miRNA deregulation in recurrent ovarian cancer, as deluded by TaqMan and immunohistochemistry.
We propose a miRNA model for the molecular pathogenesis of recurrent ovarian cancer. Some of the differentially deregulated miRNAs identified correlate with our previous transcriptome findings. Based on integrated transcriptome and miRNA analysis, miR-9 and miR-223 can be of potential importance as biomarkers in recurrent ovarian cancer.
微小RNA（miRNA）是一类小的非编码RNA，通过与靶mRNA结合来负向调节基因表达。miRNA在复发性卵巢癌（一种无法治愈的疾病）中尚未得到全面研究。
使用实时逆转录聚合酶链反应（RT-PCR），我们在先前用于转录组分析的一部分样本中，获得了原发性和复发性浆液性乳头状卵巢腺癌（n = 6）之间不同的miRNA表达谱。使用TaqMan PCR在独立的新鲜冷冻（n = 18）和福尔马林固定石蜡包埋（FFPE）浆液性卵巢肿瘤队列（n = 22）中检测了上调最明显的miRNA基因miR-223和miR-9的表达水平。在训练队列和独立测试队列之间，TaqMan分析观察到miR-223和miR-9的一致性。对上述miRNA“复发转移特征”的靶标预测分析确定了先前在我们的转录组研究中得到验证的基因。miR-9和miR-223预测靶基因列表共享了在卵巢癌中特征明确的常见生物学途径。我们提供了强有力的证据表明，miR-9在复发性卵巢癌中作为一种假定的肿瘤抑制基因发挥作用。正如TaqMan和免疫组织化学所证实的，miRNA加工机制的组成部分，如Dicer和Drosha，与复发性卵巢癌中miRNA的失调无关。
我们提出了一个关于复发性卵巢癌分子发病机制的miRNA模型。一些鉴定出的差异失调miRNA与我们之前的转录组研究结果相关。基于整合的转录组和miRNA分析，miR-9和miR-223作为复发性卵巢癌的生物标志物可能具有潜在重要性。
