Deregulation of small non-coding RNAs at the DLK1-DIO3 imprinted locus predicts lung cancer patient outcome.
Deregulation of small non-coding RNAs at the DLK1-DIO3 imprinted locus predicts lung cancer patient outcome.
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DOI：
10.18632/oncotarget.13133
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发表时间：
2016-12-06
期刊：
影响因子：
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通讯作者：
Lam WL
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文献类型：
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作者：
Enfield KS;Martinez VD;Marshall EA;Stewart GL;Kung SH;Enterina JR;Lam WL
染色体14q32.1-14q32.31上印记的DLK1-dio3基因座的失控与发育和呼吸系统疾病有关，包括癌症。在肺癌中，最近在吸烟者中描述了DLK1-dio3印记的解除调控。映射到该基因座的microRNA(MiRNA)簇的非调控表达也与患者的预后相关，这表明该基因座对肺癌疾病表型的重要性。DLK1-dio3基因座很复杂，除了编码长短的非编码RNA外，还编码多个蛋白质编码基因。虽然miRNAs的作用已经确定，但另一类相关的小RNAs-PIWI相互作用RNAs(PiRNAs)的生物学重要性尚未被研究。当在体内表达时，piRNAs通过DNA甲基化来调节基因转录。有趣的是，它们的表达模式已经被观察到在癌症中发生改变，并与患者的预后相关。在这里，我们描述了DLK1-dio3编码的piRNAs在肺腺癌和肺鳞癌两个独立队列中的体细胞表达，并研究了它们与患者预后的关系。我们发现，在DLK1-Dio3编码的piRNAs的表达增强了针对该基因座的小非编码RNA在预测患者预后方面的预后潜力，进一步强调了该基因座调控在肺癌中的重要性。
Deregulation of the imprinted DLK1-DIO3 locus at chromosome 14q32.1-14q32.31 has been associated with developmental and respiratory disorders, including cancer. In lung cancer, deregulation of imprinting at DLK1-DIO3 was recently described in smokers. Deregulated expression of a microRNA (miRNA) cluster mapping to this locus was also associated with patient outcome, suggesting the importance of this locus to lung cancer disease phenotypes. The DLK1-DIO3 locus is complex, and encodes several protein-coding genes, in addition to long and short non-coding RNAs. While the role of miRNAs is established, the biological importance of another relevant class of small RNAs, PIWI-interacting RNAs (piRNAs), has not been investigated. When somatically expressed, piRNAs regulate gene transcription through DNA methylation. Interestingly, their expression patterns have been observed to be altered in cancer and correlated with patient outcome. Here, we characterize the somatic expression of piRNAs encoded at DLK1-DIO3 in two independent cohorts of lung adenocarcinoma and lung squamous cell carcinoma and investigate their associations with patient outcome. We find that the expression of piRNAs encoded at DLK1-DIO3 enhances the prognostic potential of small non-coding RNAs specific to this locus in predicting patient outcome, further emphasizing the importance of regulation at this locus in lung cancer.