LncRNA LOC653786 promotes growth of RCC cells via upregulating FOXM1.
LncRNA LOC653786 promotes growth of RCC cells via upregulating FOXM1.
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LncRNA LOC653786 通过上调 FOXM1 促进 RCC 细胞生长
DOI：
10.18632/oncotarget.24027
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发表时间：
2018-02-23
期刊：
影响因子：
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通讯作者：
He, Fengtian
中科院分区：
文献类型：
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作者：
Yang, Fan;Wu, Qingjian;He, Fengtian
肾细胞癌（Renal cell carcinoma，RCC）是最常见的肾脏恶性肿瘤，预后差.最近，长链非编码RNA（lncRNA）已被证明是包括RCC在内的多种癌症的重要调控因子。LOC 653786是一种lncRNA，但其在癌症中的作用尚不清楚。本研究首次发现LOC 653786在肾细胞癌组织和细胞系中表达上调，并且这种lncRNA促进了肾细胞癌细胞的生长和细胞周期进程。此外，我们发现LOC 653786在RCC细胞中增加叉头框M1（FOXM 1）及其下游靶基因cyclin D1和cyclin B1的表达。报告基因分析表明，LOC 653786增强了FOXM 1基因启动子的转录活性。此外，FOXM 1的敲低减弱了RCC细胞的LOC 653786增强的生长和细胞周期进程。同时，LOC 653786的沉默抑制了RCC细胞的生长和细胞周期进程，FOXM 1的过表达减轻了这种抑制。裸鼠体内实验显示，LOC 653786的敲低抑制了异种移植肿瘤生长和FOXM 1表达。总之，我们的研究结果表明，LOC 653786通过上调FOXM 1加速RCC细胞的生长和细胞周期进程，这表明“LOC 653786/FOXM 1”通路可能作为RCC治疗的新靶点。
Renal cell carcinoma (RCC) is the most common kidney malignancy with poor prognosis. Recently, long noncoding RNAs (lncRNAs) have been demonstrated as important regulators in multiple cancers including RCC. LOC653786 is a lncRNA, but its role in cancer remains unclear. In this study, we for the first time found that LOC653786 was upregulated in RCC tissues and cell lines, and this lncRNA promoted growth and cell cycle progression of RCC cells. Moreover, we showed that LOC653786 elevated the expression of forkhead box M1 (FOXM1) and its downstream target genes cyclin D1 and cyclin B1 in RCC cells. Reporter assay revealed that LOC653786 enhanced the transcriptional activity of FOXM1 gene promoter. Additionally, knockdown of FOXM1 attenuated the LOC653786-enhanced growth and cell cycle progression of RCC cells. Meanwhile, silencing of LOC653786 suppressed RCC cell growth and cell cycle progression, which was alleviated by overexpression of FOXM1. The in vivo experiments in nude mice showed knockdown of LOC653786 repressed xenograft tumor growth and FOXM1 expression. In conclusion, our results demonstrate that LOC653786 accelerates growth and cell cycle progression of RCC cells via upregulating FOXM1, suggesting that the ‘LOC653786/FOXM1’ pathway may serve as a novel target for RCC treatment.