He Wang, Cai Qingqing, Sun Fenyong, Zhong Guangzheng, Wang Pei, Liu Hongyan, Luo Junhua, Yu Hao, Huang Jian, Lin Tianxin
Department of Urology, Sun Yat-sen Memorial Hospital, Guangzhou, People's Republic of China.
Biochim Biophys Acta. 2013 Oct;1832(10):1528-37. doi: 10.1016/j.bbadis.2013.05.010. Epub 2013 May 18.
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.
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.
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.
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.
人类基因组编码许多长链基因间非编码RNA（lincRNA）。然而，它们与膀胱癌相关的生物学功能、分子机制及预后价值仍有待阐明。在此，我们研究了一种名为linc-UBC1（膀胱癌上调1）的lincRNA，并评估了其在膀胱癌患者中的预后价值。
通过定量逆转录PCR（qRT-PCR）评估102例膀胱癌组织样本及癌旁正常组织中linc-UBC1的表达。采用体外和体内敲低策略评估linc-UBC1对细胞增殖、迁移、侵袭、集落形成、致瘤性和转移潜能的作用。进行RNA免疫沉淀（RIP）以证实linc-UBC1与多梳抑制复合物2（PRC2）的核心成分EZH2和SUZ12存在物理关联。进行染色质免疫沉淀（ChIP）以检测组蛋白修饰状态。
qRT-PCR证实，与癌旁正常组织相比，膀胱癌组织中有60例（58.8%）linc-UBC1表达上调，其过表达与淋巴结转移及不良生存相关。进一步的功能分析表明，敲低linc-UBC1可减弱膀胱癌细胞的增殖、运动、侵袭、集落形成能力、致瘤性和转移潜能。重要的是，在从患者获取的原发性膀胱癌细胞中也观察到linc-UBC1对细胞增殖的抑制作用。RIP和ChIP分析证实linc-UBC1与PRC2复合物存在物理关联，并调节靶基因的组蛋白修饰状态。
经常过表达的linc-UBC1与PRC2复合物存在物理关联，并作为膀胱癌淋巴结转移和生存的负性预后因素。
