E2F1 acts as a negative feedback regulator of c-Myc‑induced hTERT transcription during tumorigenesis.
E2F1 acts as a negative feedback regulator of c-Myc‑induced hTERT transcription during tumorigenesis.
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DOI：
10.3892/or.2014.3287
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发表时间：
2014-09
期刊：
影响因子：
4.2
通讯作者：
Yafei Zhang;Anran Zhang;Caifei Shen;Bicheng Zhang;Z. Rao;Rong-quan Wang;Shiming Yang;Shoubin Ning;Gaoping Mao;D. Fang
中科院分区：
文献类型：
--
作者：
Yafei Zhang;Anran Zhang;Caifei Shen;Bicheng Zhang;Z. Rao;Rong-quan Wang;Shiming Yang;Shoubin Ning;Gaoping Mao;D. Fang
Since induction of hTERT expression and subsequent telomerase activation play a critical role in the multistep process of tumorigenesis, a better understanding of hTERT regulation may provide not only a rationale for the molecular basis of cancer progression but also a path to the development of cancer prevention. The c-Myc oncoprotein can function effectively in activating the transcriptional expression of hTERT through E-box elements on its promoter. E2F transcription factor 1 (E2F1) was found to be a repressor of hTERT transcription by directly binding to its promoter, thereby inhibiting hTERT protein expression. For the extensively crosstalk between c-Myc and E2F1 signals, which is now known to be vital to cell fate, we speculated that E2F1 may play a negative regulatory role in c-Myc-induced hTERT transcription. In the present study, we chose to use human embryonic fibroblast cells as an experimental model system, and present evidence that the E2F1 transcription factor constitutes a negative regulatory system to limit c-Myc transcriptional activation of hTERT in normal cells. Furthermore, we demonstrated that upregulation of the miR-17-92 cluster (miR-20a/miR-17-5p) is involved in the regulation of E2F1-mediated negative feedback of the c-Myc/hTERT pathway. Our results not only reveal novel insights into how normal cells control the transmission of c-Myc-mediated oncogenic signals, but also further establish E2F1 as an important molecular target for cancer therapy.
