E2F1 acts as a negative feedback regulator of c-Myc‑induced hTERT transcription during tumorigenesis

Zhang,Yafei; Zhang,Anran; Shen,Caifei; Zhang,Bicheng; Rao,Zhiguo; Wang,Rongquan; Yang,Shiming; Ning,Shoubin; Mao,Gaoping; Fang,Dianchun

doi:10.3892/or.2014.3287

E2F1 acts as a negative feedback regulator of c-Myc‑induced hTERT transcription during tumorigenesis

Authors:
- Yafei Zhang
- Anran Zhang
- Caifei Shen
- Bicheng Zhang
- Zhiguo Rao
- Rongquan Wang
- Shiming Yang
- Shoubin Ning
- Gaoping Mao
- Dianchun Fang
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Affiliations: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P.R. China, Department of Oncology, Wuhan General Hospital of Guangzhou Command, People's Liberation Army, Wuhan, P.R. China, Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, P.R. China, Department of Gastroenterology, Air Force General Hospital of Chinese PLA, Beijing, P.R. China
Published online on: June 24, 2014 https://doi.org/10.3892/or.2014.3287
Pages: 1273-1280

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Abstract

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.

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