Replication Study: Transcriptional amplification in tumor cells with elevated c-Myc

Replication Study: Transcriptional amplification in tumor cells with elevated c-Myc
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DOI:
10.7554/elife.30274
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发表时间:
2018-01-09
期刊:
影响因子:
7.7
通讯作者:
Blum, David
Blum, David
中科院分区:
生物学1区
文献类型:
--
作者:
Lewis, L. Michelle;Edwards, Meredith C.;Blum, David

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作为可重复性项目:癌症生物学的一部分,我们发表了一份注册报告(Blum et al., 2015),描述了我们打算如何复制论文“c-Myc升高的肿瘤细胞中的转录扩增”(Lin et al., 2012)中的选定实验。我们在此报道结果。我们发现c-Myc过表达增加了P493-6 Burkitts淋巴瘤细胞中RNA的总水平;然而,虽然该效应与原始研究的方向相同(图3E; Lin et al., 2012),但在原始研究和本重复试验中测试的两批不同的血清之间,其统计显著性和效应的大小有所不同。对c-Myc过表达前后的P493-6细胞进行了一组基因的数字表达分析。在c-Myc诱导前具有活性的基因转录本在c-Myc过表达后表达增加,与原始研究相似(图3F; Lin et al., 2012)。在c-Myc诱导前沉默基因的转录本在c-Myc过表达后也会增加表达,而原始研究得出的结论是,升高的c-Myc对沉默基因没有影响(图3F; Lin et al., 2012)。将数据配对处理后,我们发现在c-Myc诱导后,活性基因和沉默基因的基因表达均有统计学意义上的显著增加,活性基因的基因表达变化大于沉默基因。最后,我们报告了每个结果的荟萃分析。
As part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Blum et al., 2015), that described how we intended to replicate selected experiments from the paper 'Transcriptional amplification in tumor cells with elevated c-Myc' (Lin et al., 2012). Here we report the results. We found overexpression of c-Myc increased total levels of RNA in P493-6 Burkitts lymphoma cells; however, while the effect was in the same direction as the original study (Figure 3E; Lin et al., 2012), statistical significance and the size of the effect varied between the original study and the two different lots of serum tested in this replication. Digital gene expression analysis for a set of genes was also performed on P493-6 cells before and after c-Myc overexpression. Transcripts from genes that were active before c-Myc induction increased in expression following c-Myc overexpression, similar to the original study (Figure 3F; Lin et al., 2012). Transcripts from genes that were silent before c-Myc induction also increased in expression following c-Myc overexpression, while the original study concluded elevated c-Myc had no effect on silent genes (Figure 3F; Lin et al., 2012). Treating the data as paired, we found a statistically significant increase in gene expression for both active and silent genes upon c-Myc induction, with the change in gene expression greater for active genes compared to silent genes. Finally, we report meta-analyses for each result.