Long noncoding RNA CRNDE stabilized by hnRNPUL2 accelerates cell proliferation and migration in colorectal carcinoma via activating Ras/MAPK signaling pathways.
Long noncoding RNA CRNDE stabilized by hnRNPUL2 accelerates cell proliferation and migration in colorectal carcinoma via activating Ras/MAPK signaling pathways.
复制标题
hnRNPUL2 稳定的长非编码 RNA CRNDE 通过激活 Ras/MAPK 信号通路加速结直肠癌细胞增殖和迁移
DOI：
10.1038/cddis.2017.258
复制
发表时间：
2017-06-08
影响因子：
9
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Jiang H;Wang Y;Ai M;Wang H;Duan Z;Wang H;Zhao L;Yu J;Ding Y;Wang S
最近的研究加深了我们对长非编码RNA(LncRNAs)在包括癌症在内的许多生物过程中的功能的理解。本研究采用实时荧光定量RT-PCR和原位杂交技术检测了结直肠癌组织和细胞中一种新的转录因子--结直肠癌差异表达核糖核酸(CRNDE)的表达，并通过一系列体内外实验研究其生物学功能，以确定其作为预后标志物和治疗靶点的可能性。CRNDE在原发结直肠癌组织和细胞中呈上调表达(P=0.002)，与肿瘤分期有关(P<0.05)，与预后不良有关(P=0.05)。通过功能获得和功能丧失实验，证实了CRNDE对结直肠癌细胞增殖、细胞周期和转移的促进作用。从机制上讲，CRNDE可以与异质性核糖核蛋白U-like 2蛋白(HnRNPUL2)形成功能复合体，并指导hnRNPUL2在细胞核和细胞质之间的转运。积累在细胞质中的hnRNPUL2在物理和功能上都能与CRNDE相互作用，增加CRNDE RNA的稳定性。此外，基因表达谱数据显示，细胞中CRNDE缺失下调了一系列涉及RAS/丝裂原活化蛋白激酶信号通路的基因。总之，这些发现为了解lncRNA CRNDE在结直肠癌发病机制中的作用和机制提供了新的见解，并突出了其作为结直肠癌干预治疗靶点的潜力。
Recent studies have furthered our understanding of the function of long noncoding RNAs (lncRNAs) in numerous biological processes, including cancer. This study investigated the expression of a novel lncRNA, colorectal neoplasia differentially expressed (CRNDE), in colorectal carcinoma (CRC) tissues and cells by real-time RT-PCR and in situ hybridization, and its biological function using a series of in vitro and in vivo experiments to determine its potential as a prognostic marker and therapeutic target. CRNDE was found to be upregulated in primary CRC tissues and cells (P< 0.05), and the upregulation of CRNDE expression is a powerful predictor of advanced TNM stage (P< 0.05) and poor prognosis for CRC patients (P= 0.002). The promoting effects of CRNDE on the cell proliferation, cell cycling and metastasis of CRC cells were confirmed both in vitro and in vivo by gain-of-function and loss-of-function experiments. Mechanistically, it was demonstrated that CRNDE could form a functional complex with heterogeneous nuclear ribonucleoprotein U-like 2 protein (hnRNPUL2) and direct the transport of hnRNPUL2 between the nucleus and cytoplasm. hnRNPUL2 that was accumulated in the cytoplasm could interact with CRNDE both physically and functionally, increasing the stability of CRNDE RNA. Moreover, gene expression profile data showed that CRNDE depletion in cells downregulated a series of genes involved in the Ras/mitogen-activated protein kinase signaling pathways. Collectively, these findings provide novel insights into the function and mechanism of lncRNA CRNDE in the pathogenesis of CRC and highlight its potential as a therapeutic target for CRC intervention.
登录
查看更多内容
影响因子：
64.5
作者：
Huarte M;Guttman M;Feldser D;Garber M;Koziol MJ;Kenzelmann-Broz D;Khalil AM;Zuk O;Amit I;Rabani M;Attardi LD;Regev A;Lander ES;Jacks T;Rinn JL
通讯作者：
Rinn JL
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
8
作者：
Cidre-Aranaz, F.;Gruenewald, T. G. P.;Alonso, J.
通讯作者：
Alonso, J.
DOI：
10.1007/978-0-387-77374-2_8
发表时间：
2007-01-01
期刊：
ALTERNATIVE SPLICING IN THE POSTGENOMIC ERA
影响因子：
--
作者：
Martinez-Contreras, Rebeca;Cloutier, Philippe;Chabot, Benoit
通讯作者：
Chabot, Benoit
影响因子：
4.8
作者：
Mahon, ES;Hawrysh, AD;Anderson, DH
通讯作者：
Anderson, DH