linc-UBC1 physically associates with polycomb repressive complex 2 (PRC2) and acts as a negative prognostic factor for lymph node metastasis and survival in bladder cancer

Objectives: The human genome encodes many long intergenic noncoding RNAs (lincRNAs). However, their biological functions, molecular mechanisms and prognostic values associated with bladder cancer remain to be elucidated. Here we investigated a lincRNA termed linc-UBC1 (Up-regulated in bladder cancer 1) and evaluated its prognostic value in bladder cancer patients.

Materials and methods: Expression of linc-UBC1 was evaluated by quantitative reverse transcription PCR (qRT-PCR) in 102 bladder cancer tissue samples and normal adjacent tissues. The functions of linc-UBC1 on cell proliferation, migration, invasion, colony formation, tumorigenicity and metastatic potential were evaluated by knockdown strategy in vitro and in vivo. RNA immunoprecipitation (RIP) was performed to confirm that linc-UBC1 physically associates with EZH2 and SUZ12, core components of polycomb repressive complex 2 (PRC2). Chromatin immunoprecipitation (ChIP) was conducted to examine histone modification status.

Results: qRT-PCR confirmed that linc-UBC1 expression is up-regulated in 60 cases (58.8%) in bladder cancer tissues compared with normal adjacent tissues, and its overexpression correlates with lymph node metastasis and poor survival. Further functional analysis demonstrated that knockdown of linc-UBC1 attenuates bladder cancer cell proliferation, motility, invasion, colony formation ability, tumorigenicity and metastatic potential. Importantly, the inhibitory effect of linc-UBC1 on cell proliferation was also observed in primary bladder cancer cells obtained from patients. RIP and ChIP assay confirmed that linc-UBC1 physically associates with PRC2 complex and regulates histone modification status of target genes.

Conclusions: Frequently overexpressed linc-UBC1 physically associates with PRC2 complex, and acts as a negative prognostic factor for lymph node metastasis and survival in bladder cancer.