title: A let-7/Fas double-negative feedback loop regulates human colon carcinoma cells sensitivity to Fas-related apoptosis.
abstract: Interferon-γ (IFN-γ) is considered essential for the regulation of anti-tumor reactions as it sensitizes Fas-related apoptosis in HT29 cells, but the mechanism is unclear. In the current study, our data demonstrated that IFN-γ stimulation and Fas activation suppressed Dicer processing and let-7 microRNA biogenesis, while let-7 microRNA strongly inhibited Fas expression by directly targeting Fas mRNA. Accordingly, our results indicate that Fas and let-7 microRNAs form a double-negative feedback loop in IFN-γ and Fas induced apoptosis in colon carcinoma cell line HT29, which may be an important synergistic mechanism in anti-tumor immune response. We also found that a let-7 microRNA inhibitor increased Fas expression and sensitized cells to Fas-related apoptosis, which may have future implications in colon carcinoma therapy.
authors.affiliation: The Department of Special Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 225, Changhai Road, Shanghai 200438, China.
authors.forename: Li
authors.initials: L
authors.lastname: Geng
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
authors.forename: Bing-Hua
authors.initials: BH
authors.lastname: Dai
authors.forename: Cheng-Jun
authors.initials: CJ
authors.lastname: Sui
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Tong
authors.initials: T
authors.lastname: Kan
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Shen
authors.forename: Jia-Mei
authors.initials: JM
authors.lastname: Yang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D002277:Carcinoma / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology*; D025461:Feedback, Physiological; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019014:fas Receptor / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C491901:FAS protein, human; D035683:MicroRNAs; D019014:fas Receptor; C487931:mirnlet7 microRNA, human; D007371:Interferon-gamma