Transcribed ultraconserved region 339 promotes carcinogenesis by sequestering tumor suppressor microRNAs

The transcribed ultraconserved regions (T-UCRs) are a family of long non-coding RNAs implicated in human carcinogenesis. The mechanism of action of T-UCRs and the factors regulating their expression in human cancers are poorly understood. In this study we show that high expression of uc.339 correlates with lower survival in 204 non-small cell lung cancer (NSCLC) patients. We also show that uc.339 found up-regulated in archival NSCLC samples, functions as a decoy for miR-339-3p, -663-3p and -95-5p. As a result, Cyclin E2, a direct target of these microRNAs is up-regulated, promoting cancer growth and migration. We provide evidence from cell lines and primary samples suggesting that TP53 directly regulates uc.339. Our results support a key role for uc.339 in lung cancer. 4 experimental groups in triplicate (total: 12 samples). A339= A549 infected with a lentivirus over-expressing uc.339; AE= A549 infected with an empty lentivirus (control of A339); L339= LoVo infected with a lentivirus over-expressing uc.330; LE= LoVo infected with an empty lentivirus (control of L339). 1-2-3 refer to each experiment.