title: miR-203 is a direct transcriptional target of E2F1 and causes G1 arrest in esophageal cancer cells.
abstract: miR-203 act as tumor repressor by inhibiting cell proliferation and is repressed in a variety of human tumors, although the molecular mechanisms responsible have not been elucidated. Here, we reveal that miR-203 is regulated by E2F1, an important transcription factor that can induce cell proliferation by controlling cell cycle progression. We found that miR-203 expression was induced by cisplatin, which also induced E2F1 protein accumulation in esophageal squamous cell carcinoma (ESCC) cell lines. miR-203 expression was elevated upon activation of ectopic E2F1, whereas this induction was abolished when the E2F1 gene was silenced. Moreover, with luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays, we demonstrated that E2F1 transactivates miR-203 by directly binding to the miR-203 gene promoter. In addition, we found that miR-203 inhibited cell proliferation by inducing G1/S cell cycle arrest, but not apoptosis, in ESCC cell lines. Finally, we observed that miR-203 negatively inhibited the expression of CDK6, subsequently decreasing E2F1 expression possibly through Rb phosphorylation. Taken together, our data show that cancer-related miR-203 is a novel transcriptional target of E2F1 and that it regulates cell cycle arrest by participating in a feedback loop with E2F1.
authors.affiliation: Department of Medical Genetics, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Limeng
authors.initials: L
authors.lastname: Dai
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Xueqing
authors.initials: X
authors.lastname: Xu
authors.forename: Jiazhong
authors.initials: J
authors.lastname: Shi
authors.forename: Liyuan
authors.initials: L
authors.lastname: Fu
authors.forename: Xuedan
authors.initials: X
authors.lastname: Chen
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Bai
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics* / Q000502:physiology; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*
chemical_list: D050687:E2F1 Transcription Factor; C546703:MIRN203 microRNA, human; D035683:MicroRNAs