Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Nat Biotechnol. 2011 Jul 31;29(8):742-9. doi: 10.1038/nbt.1914.
Noncoding RNAs (ncRNAs) are emerging as key molecules in human cancer, with the potential to serve as novel markers of disease and to reveal uncharacterized aspects of tumor biology. Here we discover 121 unannotated prostate cancer-associated ncRNA transcripts (PCATs) by ab initio assembly of high-throughput sequencing of polyA(+) RNA (RNA-Seq) from a cohort of 102 prostate tissues and cells lines. We characterized one ncRNA, PCAT-1, as a prostate-specific regulator of cell proliferation and show that it is a target of the Polycomb Repressive Complex 2 (PRC2). We further found that patterns of PCAT-1 and PRC2 expression stratified patient tissues into molecular subtypes distinguished by expression signatures of PCAT-1-repressed target genes. Taken together, our findings suggest that PCAT-1 is a transcriptional repressor implicated in a subset of prostate cancer patients. These findings establish the utility of RNA-Seq to identify disease-associated ncRNAs that may improve the stratification of cancer subtypes.
非编码 RNA（ncRNA）是人类癌症中的关键分子，具有作为疾病新型标志物的潜力，并揭示肿瘤生物学的未被描述的方面。在这里，我们通过对 102 个前列腺组织和细胞系的高通量测序 polyA（+）RNA（RNA-Seq）进行从头组装，发现了 121 个未注释的前列腺癌相关 ncRNA 转录本（PCATs）。我们将一个 ncRNA，PCAT-1，鉴定为一种前列腺特异性的细胞增殖调节剂，并表明它是多梳抑制复合物 2（PRC2）的靶点。我们进一步发现，PCAT-1 和 PRC2 的表达模式将患者组织划分为分子亚型，这些亚型通过 PCAT-1 抑制靶基因的表达特征来区分。总之，我们的研究结果表明，PCAT-1 是一种转录抑制剂，可能与一部分前列腺癌患者有关。这些发现确立了 RNA-Seq 用于鉴定可能改善癌症亚型分层的疾病相关 ncRNA 的用途。
