The long noncoding RNA KCNQ1DN suppresses the survival of renal cell carcinoma cells through downregulating c-Myc
The long noncoding RNA KCNQ1DN suppresses the survival of renal cell carcinoma cells through downregulating c-Myc
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长非编码RNA KCNQ1DN通过下调c-Myc抑制肾细胞癌细胞的存活
DOI：
10.7150/jca.29280
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发表时间：
2019-08
影响因子：
3.9
通讯作者：
Zhang Kebin
中科院分区：
文献类型：
--
作者：
Yang Fan;Wu Qingjian;Zhang Le;Xie Wei;Sun Xiaoli;Zhang Yan;Wang Lei;Dai Qian;Yu Hua;Chen Qian;Sheng Halei;Qiu Jing;He Xiaomei;Miao Hongming;He Fengtian;Zhang Kebin
背景：已证实长非编码RNA(LncRNAs)在肾癌(RCC)中起重要作用。然而，LncRNA KCNQ1DN在肾癌中的作用尚不清楚。方法：采用定量聚合酶链式反应方法检测KCNQ1DN在肾癌及癌旁组织中的表达。采用RNA荧光原位杂交(FISH)、甲基化分析、报告基因检测和功能检测等方法研究KCNQ1DN对肾癌的影响。结果：在本研究中，我们发现在肾癌组织和细胞系中，lncRNA KCNQ1DN显著降低。RNA FISH分析表明，KCNQ1DN主要定位于细胞质。甲基化分析显示，肾癌组织中KCNQ1DN启动子近端区域的甲基化程度明显高于癌旁正常组织。功能研究表明，KCNQ1DN抑制肾癌细胞生长和细胞周期进程。从机制上讲，KCNQ1DN可抑制c-Myc的表达，这可能是KCNQ1DN在基因和蛋白水平进一步上调细胞周期蛋白d1和抑制p27的机制之一。报告基因分析表明，KCNQ1DN抑制了c-Myc启动子的转录活性。裸鼠体内实验表明，KCNQ1DN过表达显著抑制了移植瘤的生长及相应c-Myc的表达。结论：KCNQ1DN可能通过抑制癌基因c-myc在体内外抑制肾癌细胞的生长，有望成为治疗肾癌的新靶点。
Background: Long noncoding RNAs (lncRNAs) have been demonstrated to play essential roles in renal cell carcinoma (RCC). However, the role of lncRNA KCNQ1DN in RCC remains unclear. Methods: The expression of KCNQ1DN in RCC and the corresponding adjacent tissues was measured by qPCR. RNA fluorescence in situ hybridization (FISH) assay, methylation analysis, reporter gene assays and functional tests were performed to reveal the effects of KCNQ1DN on RCC. Results: In the present study, we found that lncRNA KCNQ1DN was notably decreased in RCC tissues and cell lines. RNA FISH assay showed that KCNQ1DN mainly localized to the cytoplasm. Methylation analysis revealed that the proximal region of KCNQ1DN promoter was hypermethylated in RCC tissues relative to the adjacent normal ones. Functional studies clarified that KCNQ1DN repressed the RCC cell growth and cell cycle progression. Mechanistically, KCNQ1DN inhibited the expression of c-Myc, which might further upregulate cyclin D1 and suppress p27 at mRNA and protein levels in RCC cells. Reporter gene assays revealed that the transcriptional activity of c-Myc promoter was inhibited by KCNQ1DN. The in vivo experiments in nude mice showed that KCNQ1DN overexpression dramatically repressed the growth of xenograft tumors and the expression of corresponding c-Myc. Conclusion: These results indicated that KCNQ1DN inhibit the growth of RCC cells in vitro and in vivo through repressing the oncogene c-myc, suggesting that KCNQ1DN may serve as a novel target for the treatment of RCC.
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影响因子：
64.8
作者：
Tseng YY;Moriarity BS;Gong W;Akiyama R;Tiwari A;Kawakami H;Ronning P;Reuland B;Guenther K;Beadnell TC;Essig J;Otto GM;O'Sullivan MG;Largaespada DA;Schwertfeger KL;Marahrens Y;Kawakami Y;Bagchi A
通讯作者：
Bagchi A
DOI：
10.1891/9780826121646.0002
发表时间：
2018-09
期刊：
Cancer Rehabilitation
影响因子：
--
作者：
K. Miller;R. Siegel;R. Khan;A. Jemal
通讯作者：
K. Miller;R. Siegel;R. Khan;A. Jemal
长非编码RNA RHPN1-AS1促进葡萄膜黑色素瘤进展
影响因子：
5.6
作者：
Lu L;Yu X;Zhang L;Ding X;Pan H;Wen X;Xu S;Xing Y;Fan J;Ge S;Zhang H;Jia R;Fan X
通讯作者：
Fan X
影响因子：
5.4
作者：
Conacci-Sorrell, Maralice;McFerrin, Lisa;Eisenman, Robert N.
通讯作者：
Eisenman, Robert N.
影响因子：
15.3
作者：
Bhatt, Jaimin R.;Finelli, Antonio
通讯作者：
Finelli, Antonio