title: MiR-145 promotes TNF-α-induced apoptosis by facilitating the formation of RIP1-FADDcaspase-8 complex in triple-negative breast cancer.
abstract: Researches indicate that the dysregulation of microRNA (miRNA) is involved in tumorigenesis. Among such dysregulated miRNAs in cancer, miR-145 is reported to be downregulated in multiple cancers. In this study, we demonstrated the downregulation of miR-145 in triple-negative breast cancer (TNBC) tissues and TNBC cell lines by quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis. Furthermore, we found that the tumor necrosis factor-alpha (TNF-α)-induced apoptosis was expanded by the transfection of miR-145 in MDA-MB-231 which belongs to the TNBC cell lines. We then indicated that the mechanism by which miR-145 promotes the TNF-α-induced apoptosis is dependent on the formation of RIP1-FADD-caspase-8 complex. The cellular inhibitor of apoptosis (cIAP1), which is the inhibitor of apoptosis protein, was found to be a target of miR-145 in MDA-MB-231 cells. As a result of cIAP1 overexpression, the promotion of miR-145 on TNF-α-induced apoptosis was inhibited in MDA-MB-231 cells. Therefore, our results indicate that miR-145 acts as a tumor suppressor in TNBC, suggesting that the miR-145-cIAP1 axis might be a potential therapeutic target for TNBC.
authors.affiliation: Department of Breast Surgery, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Breast Surgery, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Wu
authors.affiliation: School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Anqi
authors.initials: A
authors.lastname: Wu
authors.affiliation: School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Huang
authors.affiliation: School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Na
authors.initials: N
authors.lastname: He
authors.affiliation: Department of Breast Surgery, Zhejiang Provincial Hospital of Traditional Chinese Medicine, No. 54 Youdian Road, Hangzhou City, Zhejiang Province, 310006, China. hzxiaohongxie@126.com.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Xie
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D053200:Fas-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D035683:MicroRNAs / Q000235:genetics*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: C119724:AGFG1 protein, human; D014408:Biomarkers, Tumor; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D028861:Nuclear Pore Complex Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014409:Tumor Necrosis Factor-alpha; D053181:Caspase 8
keywords: RIP1-FADD-caspase-8; TNBC; TNF-α; cIAP1; miR-145