lncRNA Up-Regulated in Nonmuscle Invasive Bladder Cancer Facilitates Tumor Growth and Acts as a Negative Prognostic Factor of Recurrence
lncRNA Up-Regulated in Nonmuscle Invasive Bladder Cancer Facilitates Tumor Growth and Acts as a Negative Prognostic Factor of Recurrence
复制标题
非肌层浸润性膀胱癌中 lncRNA 上调促进肿瘤生长并作为复发的负面预后因素
DOI：
10.1016/j.juro.2016.05.107
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发表时间：
2016-10-01
影响因子：
6.6
通讯作者：
Lin, Tianxin
中科院分区：
文献类型：
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作者：
Zhang, Simin;Zhong, Guangzheng;Lin, Tianxin
目的：虽然 lncRNA（长非编码 RNA）已被证明在癌症生物学中具有关键的调节作用，但其在非肌层浸润性膀胱癌中的生物学功能和预后价值仍然很大程度上未知。我们鉴定了一种名为lncRNA-UNMIBC（在非肌层浸润性膀胱癌中上调）的lncRNA，并评估了其对原发性非肌层浸润性膀胱癌患者的预后价值。 材料与方法：我们通过实时定量聚合酶链反应分析了75例原发性非肌层浸润性膀胱癌和邻近正常粘膜组织中lncRNA-UNMIBC的表达。使用Kaplan-Meier方法和多元Cox回归分析将数据与临床病理学参数进行比较。通过在体外和体内沉默lncRNA来评估lncRNA-UNMIBC的功能。进行RNA免疫沉淀来测定lncRNA-UNMIBC是否可以与EZH2（zeste同源物2的增强子）和SUZ12（SUZ12多梳抑制复合物2亚基）物理相关，它们是PRC2（多梳抑制复合物2）的核心成分。染色质免疫沉淀检测组蛋白修饰状态。结果：45例原发性非肌层浸润性膀胱癌组织中lncRNA-UNMIBC表达水平较正常黏膜上调。 Kaplan-Meier 估计表明，lncRNA-UNMIBC 表达与复发显着相关（对数秩检验 p = 0.0151）。我们还发现 lncRNA-UNMIBC 在 G0/G1 逮捕中发挥关键作用。此外，RNA和染色质免疫沉淀分析表明lncRNA-UNMIBC与EZH2和SUZ12物理相关，导致靶基因的组蛋白H3赖氨酸27甲基化状态改变。结论：这些发现表明lncRNA-UNMIBC可以促进肿瘤生长，并可能作为复发的负面预后因素。
Purpose: While lncRNAs (long noncoding RNAs) have been shown to have critical regulatory roles in cancer biology, the biological functions and prognostic values in nonmuscle invasive bladder cancer remain largely unknown. We identified a lncRNA termed lncRNA-UNMIBC (up-regulated in nonmuscle invasive bladder cancer) and evaluated its prognostic value in patients with primary nonmuscle invasive bladder cancer.Materials and Methods: We analyzed the expression of lncRNA-UNMIBC in the tissues of 75 cases of primary nonmuscle invasive bladder cancer and adjacent normal mucosa by quantitative real-time polymerase chain reaction. Data were compared with clinicopathological parameters using the 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 was performed to assay whether lncRNA-UNMIBC could be physically associated with EZH2 (enhancer of zeste homolog 2) and SUZ12 (SUZ12 polycomb repressive complex 2 subunit), which are core components of PRC2 (polycomb repressive complex 2). Chromatin immunoprecipitation was done to examine histone modification status.Results: The expression level of lncRNA-UNMIBC was up-regulated in the tissues of 45 cases of primary nonmuscle invasive bladder cancer compared with normal mucosa. Kaplan-Meier estimates showed that lncRNA-UNMIBC expression was significantly associated with recurrence (log rank test p = 0.0151). We also found that lncRNA-UNMIBC had a key role in G0/G1 arrest. Furthermore, RNA and chromatin immunoprecipitation assays demonstrated that lncRNA-UNMIBC was physically associated with EZH2 and SUZ12, leading to an altered histone H3 lysine 27 methylation status of target genes.Conclusions: These findings indicate that lncRNA-UNMIBC can facilitate tumor growth and may act as a negative prognostic factor of recurrence.