Hsa-let-7a functions as a tumor suppressor in renal cell carcinoma cell lines by targeting c-myc
Hsa-let-7a functions as a tumor suppressor in renal cell carcinoma cell lines by targeting c-myc
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DOI：
10.1016/j.bbrc.2011.11.119
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发表时间：
2012-01-06
影响因子：
3.1
通讯作者：
Fan, Jie
中科院分区：
文献类型：
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作者：
Liu, Yongchao;Yin, Bingde;Fan, Jie
c-myc信号通路的广泛功能在肾细胞癌（RCC）的发生发展中起着至关重要的作用。因此，我们评估了肾癌细胞系中原癌基因c-myc和抗肿瘤hsa-let-7a（let-7a）之间的联系。用let-7a模拟物或阴性对照物转染肾癌细胞系769 P、Caki-1和786 O后，检测c-myc和let-7a的表达。Western blot证实c-myc蛋白水平的变化。采用细胞计数试剂盒-8（CCK-8）进行细胞增殖分析和流式细胞术进行细胞周期分析，评价let-7a的抗肿瘤作用。采用逆转录实时定量PCR（qRT-PCR）检测c-myc下游靶基因的变化。我们的研究结果首次表明let-7a通过下调c-myc和c-myc靶基因如增殖细胞核抗原（PCNA）、细胞周期蛋白D1（CCND 1）和miR 17 -92簇在RCC细胞系中起肿瘤抑制剂的作用，这伴随着增殖抑制和细胞周期停滞。(C)2011 Elsevier Inc. All rights reserved.
Widespread functions of the c-myc pathway play a crucial role in renal cell carcinoma (RCC) carcinogenesis. Thus, we evaluated the connection between proto-oncogenic c-myc and anti-neoplastic hsa-let-7a (let-7a) in RCC cell lines. The levels of c-myc and let-7a in 3 RCC cell lines (769P, Caki-1 and 786O) were measured after transfecting the cells with let-7a mimics or a negative control. The change in c-myc protein level was confirmed by Western blot. The anti-neoplastic function of let-7a was evaluated using cell counting kit-8 (CCK-8) for proliferation analysis and cell flow cytometry for cell cycle analysis. The changes of downstream targets of c-myc were measured using reverse transcription quantitative real-time PCR (qRT-PCR). Our results suggest for the first time that let-7a acts as a tumor suppressor in RCC cell lines by down-regulating c-myc and c-myc target genes such as proliferating cell nuclear antigen (PCNA), cyclin D1 (CCND1) and the miR17-92 cluster, which is accompanied by proliferation inhibition and cell cycle arrest. (C) 2011 Elsevier Inc. All rights reserved.