MiR-145 promotes TNF-α-induced apoptosis by facilitating the formation of RIP1-FADDcaspase-8 complex in triple-negative breast cancer.
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.
Mesh Terms:
Apoptosis, Biomarkers, Tumor, Blotting, Western, Caspase 8, Cell Proliferation, Fas-Associated Death Domain Protein, Female, Gene Expression Regulation, Neoplastic, Humans, Immunoenzyme Techniques, Immunoprecipitation, MicroRNAs, Nuclear Pore Complex Proteins, Prognosis, RNA, Messenger, RNA-Binding Proteins, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Triple Negative Breast Neoplasms, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha
Apoptosis, Biomarkers, Tumor, Blotting, Western, Caspase 8, Cell Proliferation, Fas-Associated Death Domain Protein, Female, Gene Expression Regulation, Neoplastic, Humans, Immunoenzyme Techniques, Immunoprecipitation, MicroRNAs, Nuclear Pore Complex Proteins, Prognosis, RNA, Messenger, RNA-Binding Proteins, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Triple Negative Breast Neoplasms, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha
Tumour Biol.
Date: Jul. 01, 2016
PubMed ID: 26733177
View in: Pubmed Google Scholar
Download Curated Data For This Publication
199403
Switch View:
- Interactions 2