lncRNA 在非肌肉浸润性膀胱癌中上调促进肿瘤生长，并作为复发的负预后因素。
lncRNA Up-Regulated in Nonmuscle Invasive Bladder Cancer Facilitates Tumor Growth and Acts as a Negative Prognostic Factor of Recurrence.
机构信息
Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
出版信息
J Urol. 2016 Oct;196(4):1270-8. doi: 10.1016/j.juro.2016.05.107. Epub 2016 Jun 5.
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.
目的
虽然长链非编码 RNA（lncRNAs）已被证明在癌症生物学中具有关键的调节作用，但在非肌肉浸润性膀胱癌中的生物学功能和预后价值仍知之甚少。我们鉴定了一种称为 lncRNA-UNMIBC（非肌肉浸润性膀胱癌中上调的长链非编码 RNA）的 lncRNA，并评估了其在原发性非肌肉浸润性膀胱癌患者中的预后价值。
材料和方法
通过实时定量聚合酶链反应分析了 75 例原发性非肌肉浸润性膀胱癌组织和相邻正常粘膜中 lncRNA-UNMIBC 的表达。通过 Kaplan-Meier 方法和多变量 Cox 回归分析将数据与临床病理参数进行比较。通过体外和体内沉默 lncRNA-UNMIBC 来评估 lncRNA-UNMIBC 的功能。进行 RNA 免疫沉淀以检测 lncRNA-UNMIBC 是否可以与 EZH2（增强子的 zeste 同源物 2）和 SUZ12（SUZ12 多梳抑制复合物 2 亚基）物理结合，EZH2 和 SUZ12 是 PRC2（多梳抑制复合物 2）的核心组成部分。进行染色质免疫沉淀以检查组蛋白修饰状态。
结果
与正常粘膜相比，45 例原发性非肌肉浸润性膀胱癌组织中 lncRNA-UNMIBC 的表达水平上调。Kaplan-Meier 估计表明，lncRNA-UNMIBC 的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 期阻滞中起关键作用。此外，RNA 和染色质免疫沉淀试验表明，lncRNA-UNMIBC 与 EZH2 和 SUZ12 物理结合，导致靶基因的组蛋白 H3 赖氨酸 27 甲基化状态发生改变。
结论
这些发现表明，lncRNA-UNMIBC 可以促进肿瘤生长，并且可能是复发的负预后因素。
Zotero 插件