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Long noncoding RNAs (lncRNAs) have been shown to play critical regulatory roles in cancer biology. However, their biological functions and prognostic values in Nonmuscle Invasive Bladder Cancer (NMIBC) remain largely unknown. Here we identified a lncRNA termed lncRNA-UNMIBC (Up-regulated in NMIBC) and evaluated its prognostic value in primary NMIBC patients.

We analyzed the expression of lncRNA-UNMIBC in 75 cases of primary NMIBC tissues and adjacent normal mucosa tissues (NMTs) by quantitative real-time PCR (qRT-PCR). Data were compared with clinicopathological parameters using Kaplan-Meier method and multivariate Cox regression analysis. The functions of lncRNA-UNMIBC were assessed by silencing the lncRNA in vitro and in vivo. RNA immunoprecipitation (RIP) was performed to assay if lncRNA-UNMIBC could physically associate with enhancer of zeste homolog 2 (EZH2) and SUZ12 polycomb repressive complex 2 subunit (SUZ12), core components of polycomb repressive complex 2(PRC2). Chromatin immunoprecipitation (ChIP) was conducted to examine histone modification status.

The expression level of lncRNA-UNMIBC was up-regulated in 45 cases of primary NMIBC tissues compared with NMTs. Kaplan-Meier estimates showed lncRNA-UNMIBC expression was significantly associated with recurrence (log rank test, p = 0.0151). We also found that lncRNA-UNMIBC played a key role in G0/G1 arrest. Furthermore, RIP and ChIP assays demonstrated that lncRNA-UNMIBC physically associated with EZH2 and SUZ12, leading to altered histone H3 lysine 27 methylation status of target genes.

These findings indicate that lncRNA-UNMIBC can facilitate tumor growth and may act as a negative prognostic factor of recurrence.

Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

PMID:27267320