Potential cancer-related role of circadian gene TIMELESS suggested by expression profiling and in vitro analyses.
Potential cancer-related role of circadian gene TIMELESS suggested by expression profiling and in vitro analyses.
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DOI：
10.1186/1471-2407-13-498
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发表时间：
2013-10-25
期刊：
影响因子：
3.8
通讯作者：
Zhu Y
中科院分区：
文献类型：
--
作者：
Mao Y;Fu A;Leaderer D;Zheng T;Chen K;Zhu Y
生物钟和细胞周期是两个全球性的调控系统，对真核细胞具有普遍的行为和生理影响，并且在癌症的发展中都起作用。最近的研究表明，昼夜节律和细胞周期调节剂TIMELESS可能是这两个调节系统之间的分子桥梁。为了评估TIMELESS在肿瘤发生中的作用，我们分析了来自公开在线数据库的TIMELESS表达数据。然后使用无时间性靶向siRNA寡核苷酸进行功能丧失分析，然后进行全基因组表达微阵列和网络分析。根据我们的网络分析结果，我们进一步测试了TIMELESS下调对乳腺癌和宫颈癌细胞系细胞增殖率的影响。与正常对照相比，发现TIMELESS在不同肿瘤类型中经常过表达。TIMELESS表达升高与肿瘤分期越晚、乳腺癌预后越差有显著相关性。我们发现了一个与癌症相关的转录本网络，其表达在TIMELESS敲除后发生改变，其中包含许多在癌症发生和进展中具有已知功能的基因。此外，我们观察到，敲除TIMELESS可显著降低细胞增殖率。我们的研究结果表明，TIMELESS在肿瘤发生中的潜在作用，值得进一步研究其表达作为癌症易感性和预后结果的潜在生物标志物。
The circadian clock and cell cycle are two global regulatory systems that have pervasive behavioral and physiological effects on eukaryotic cells, and both play a role in cancer development. Recent studies have indicated that the circadian and cell cycle regulator, TIMELESS, may serve as a molecular bridge between these two regulatory systems. To assess the role of TIMELESS in tumorigenesis, we analyzed TIMELESS expression data from publically accessible online databases. A loss-of-function analysis was then performed using TIMELESS-targeting siRNA oligos followed by a whole-genome expression microarray and network analysis. We further tested the effect of TIMELESS down-regulation on cell proliferation rates of a breast and cervical cancer cell line, as suggested by the results of our network analysis. TIMELESS was found to be frequently overexpressed in different tumor types compared to normal controls. Elevated expression of TIMELESS was significantly associated with more advanced tumor stage and poorer breast cancer prognosis. We identified a cancer-relevant network of transcripts with altered expression following TIMELESS knockdown which contained many genes with known functions in cancer development and progression. Furthermore, we observed that TIMELESS knockdown significantly decreased cell proliferation rate. Our results suggest a potential role for TIMELESS in tumorigenesis, which warrants further investigation of TIMELESS expression as a potential biomarker of cancer susceptibility and prognostic outcome.
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影响因子：
5.2
作者：
Cho YG;Chang X;Park IS;Yamashita K;Shao C;Ha PK;Pai SI;Sidransky D;Kim MS
通讯作者：
Kim MS
影响因子：
30.8
作者：
Carroll, Jason S.;Meyer, Clifford A.;Brown, Myles
通讯作者：
Brown, Myles
影响因子：
6.4
作者：
BRAVARD, A;SABATIER, L;DUTRILLAUX, B
通讯作者：
DUTRILLAUX, B
影响因子：
8
作者：
Kim, TH;Xiong, H;Ren, B
通讯作者：
Ren, B
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y