Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs.
Ivan VanniniPetra M WiseKishore B ChallagundlaMeropi PlousiouMirco RaffiniErika BandiniFrancesca FaniniGiorgia PaliagaMelissa CrawfordManuela FerracinCristina IvanLinda FabrisRamana V DavuluriZhiyi GuoMaria Angelica CortezXinna ZhangLu ChenShuxing ZhangCecilia Fernandez-CymeringLeng HanSilvia CarloniSamanta SalviHui LingMariam MurtadhaPaolo NevianiBarbara J GitlitzIte A Laird-OffringaPatrick Nana-SinkamMassimo NegriniHan LiangDino AmadoriAmelia CimminoGeorge A CalinMuller FabbriPublished in: Nature communications (2017)
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.
Keyphrases
- poor prognosis
- long non coding rna
- small cell lung cancer
- end stage renal disease
- endothelial cells
- cell proliferation
- chronic kidney disease
- ejection fraction
- signaling pathway
- squamous cell carcinoma
- advanced non small cell lung cancer
- binding protein
- prognostic factors
- cell cycle
- cell death
- transcription factor
- tyrosine kinase
- childhood cancer