MiR-145 promotes TNF-α-induced apoptosis by facilitating the formation of RIP1-FADDcaspase-8 complex in triple-negative breast cancer

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• 作者：Min Zheng ; Zhihao Wu ; Anqi Wu ; Zhenyu Huang ; Na He ; Xiaohong Xie
• 刊名：Tumor Biology
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：37
• 期：7
• 页码：8599-8607
• 全文大小：1,715 KB
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380
• 卷排序：37

文摘

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.KeywordsTNBCmiR-145cIAP1TNF-αRIP1-FADD-caspase-8