Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) S.r.l., IRCCS, Gene Therapy Unit, 47014, Meldola (FC), Italy.
Departments of Pediatrics and Molecular Microbiology & Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Children's Center for Cancer and Blood Diseases and The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, 90027, USA.
Nat Commun. 2017 Nov 27;8(1):1801. doi: 10.1038/s41467-017-01562-9.
The transcribed ultraconserved regions (T-UCRs) encode long non-coding RNAs implicated in human carcinogenesis. Their mechanisms of action and the factors regulating their expression in cancers are poorly understood. Here we show that high expression of uc.339 correlates with lower survival in 210 non-small cell lung cancer (NSCLC) patients. We provide evidence from cell lines and primary samples that TP53 directly regulates uc.339. We find that transcribed uc.339 is upregulated in archival NSCLC samples, functioning as a decoy RNA for miR-339-3p, -663b-3p, and -95-5p. As a result, Cyclin E2, a direct target of all these microRNAs is upregulated, promoting cancer growth and migration. Finally, we find that modulation of uc.339 affects microRNA expression. However, overexpression or downregulation of these microRNAs causes no significant variations in uc.339 levels, suggesting a type of interaction for uc.339 that we call "entrapping". Our results support a key role for uc.339 in lung cancer.
转录超保守区(T-UCRs)编码长非编码 RNA,这些 RNA 与人类致癌作用有关。其作用机制以及在癌症中调节其表达的因素知之甚少。在这里,我们显示 uc.339 的高表达与 210 名非小细胞肺癌(NSCLC)患者的生存率降低相关。我们通过细胞系和原发性样本提供了证据,证明 TP53 直接调节 uc.339。我们发现转录的 uc.339 在存档的 NSCLC 样本中上调,作为 miR-339-3p、-663b-3p 和 -95-5p 的诱饵 RNA。结果,Cyclin E2,这些 miRNA 的直接靶标上调,促进癌症生长和迁移。最后,我们发现 uc.339 的调节会影响 microRNA 的表达。然而,这些 microRNAs 的过表达或下调不会导致 uc.339 水平发生显著变化,这表明我们称之为“捕获”的 uc.339 相互作用类型。我们的结果支持 uc.339 在肺癌中的关键作用。