title: E2F1 acts as a negative feedback regulator of c-Myc‑induced hTERT transcription during tumorigenesis.
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.
authors: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P.R. China.
authors: Yafei
authors: Y
authors: Zhang
authors: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P.R. China.
authors: Anran
authors: A
authors: Zhang
authors: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P.R. China.
authors: Caifei
authors: C
authors: Shen
authors: Department of Oncology, Wuhan General Hospital of Guangzhou Command, People's Liberation Army, Wuhan, P.R. China.
authors: Bicheng
authors: B
authors: Zhang
authors: Department of Oncology, Wuhan General Hospital of Guangzhou Command, People's Liberation Army, Wuhan, P.R. China.
authors: Zhiguo
authors: Z
authors: Rao
authors: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P.R. China.
authors: Rongquan
authors: R
authors: Wang
authors: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, P.R. China.
authors: Shiming
authors: S
authors: Yang
authors: Department of Gastroenterology, Air Force General Hospital of Chinese PLA, Beijing, P.R. China.
authors: Shoubin
authors: S
authors: Ning
authors: Department of Gastroenterology, Air Force General Hospital of Chinese PLA, Beijing, P.R. China.
authors: Gaoping
authors: G
authors: Mao
authors: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P.R. China.
authors: Dianchun
authors: D
authors: Fang
mesh_terms: D017209:Apoptosis; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D008954:Models, Biological; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C568997:MIR17HG, human; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding; C509186:TERT protein, human; D019098:Telomerase