Knockdown of miR-182 promotes apoptosis via regulating RIP1 deubiquitination in TNF-α-treated triple-negative breast cancer cells.
Overexpression of microRNA-182 (miR-182) is found in multiple cancers, but the association of miR-182 expression with the sensitivity of triple-negative breast cancer (TNBC) cells to tumor necrosis factor-alpha (TNF-α) remains unknown. In this study, up-regulation of miR-182 was validated in TNBC patients and cell lines. Knockdown of miR-182 was observed ... to hinder the proliferation of BT-549 cells. More importantly, knockdown of miR-182 significantly promoted the apoptosis induced by TNF-α treatment in BT-549. JC-1 staining and western blot assays revealed that the K63-linked ubiquitin chains on receptor-interacting protein 1 (RIP1) were removed and the outer mitochondrial membrane potential (MMP) and permeability was altered upon combination of TNF-α with anti-miR-182. We then demonstrated that knockdown of miR-182 up-regulated the expression of cylindromatosis (CYLD) deubiquitinase, which promoted the formation of death-inducing signaling complex (DISC) and subsequent caspase-8 activation in TNF-α-treated BT-549 cells. Collectively, the results of the present study improve our understanding of the role of miR-182 in TNBC, knockdown of which facilitates the degradation of ubiquitin chains on RIP1, leading to the caspase-8 activation and apoptosis in TNF-α-treated TNBC cells. This may be valuable for the development of cancer therapy.
Mesh Terms:
Apoptosis, Biomarkers, Tumor, Blotting, Western, Cell Proliferation, Female, Flow Cytometry, Gene Expression Regulation, Neoplastic, Humans, Immunoenzyme Techniques, Immunoprecipitation, MicroRNAs, Neoplasm Staging, 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, Ubiquitin, Ubiquitination
Apoptosis, Biomarkers, Tumor, Blotting, Western, Cell Proliferation, Female, Flow Cytometry, Gene Expression Regulation, Neoplastic, Humans, Immunoenzyme Techniques, Immunoprecipitation, MicroRNAs, Neoplasm Staging, 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, Ubiquitin, Ubiquitination
Tumour Biol.
Date: Oct. 01, 2016
PubMed ID: 27476169
View in: Pubmed Google Scholar
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