國家衛生研究院 NHRI:Item 3990099045/12404
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12404


    Title: MCP-1/MCPIP-1 signaling modulates the effects of IL-1beta in renal cell carcinoma through ER stress-mediated apoptosis
    Other Titles: MCP-1/MCPIP-1 signaling modulates the effects of IL-1β in renal cell carcinoma through ER stress-mediated apoptosis
    Authors: Lee, CH;Hung, PF;Lu, SC;Chung, HL;Chiang, SL;Wu, CT;Chou, WC;Sun, CY
    Contributors: National Institute of Cancer Research
    Abstract: In renal cell carcinoma (RCC), interleukin (IL)-1beta may be a pro-metastatic cytokine. However, we have not yet noted the clinical association between tumoral expression or serum level of IL-1beta and RCC in our patient cohort. Herein, we investigate molecular mechanisms elicited by IL-1beta in RCC. We found that IL-1beta stimulates substantial monocyte chemoattractant protein (MCP)-1 production in RCC cells by activating NF-kB and AP-1. In our xenograft RCC model, intra-tumoral MCP-1 injection down-regulated Ki67 expression and reduced tumor size. Microarray analysis revealed that MCP-1 treatment altered protein-folding processes in RCC cells. MCP-1-treated RCC cells and xenograft tumors expressed MCP-1-induced protein (MCPIP) and molecules involved in endoplasmic reticulum (ER) stress-mediated apoptosis, namely C/EBP Homologous Protein (CHOP), protein kinase-like ER kinase (PERK), and calnexin (CNX). ER stress-mediated apoptosis in MCP-1-treated RCC cells was confirmed using Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay. Moreover, ectopic MCPIP expression increased PERK expression in Human embryonic kidney (HEK)293 cells. Our meta-analysis revealed that low MCP-1 levels reduce 1-year post-nephrectomy survival in patients with RCC. Immunohistochemistry indicated that in some RCC biopsy samples, the correlation between MCP-1 or MCPIP expression and tumor stages was inverse. Thus, MCP-1 and MCPIP potentially reduce the IL-1beta-mediated oncogenic effect in RCC; our findings suggest that ER stress is a potential RCC treatment target.
    Date: 2019-12-03
    Relation: International Journal of Molecular Sciences. 2019 Dec 3;20(23):Article number 6101.
    Link to: http://dx.doi.org/10.3390/ijms20236101
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1422-0067&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000504428300283
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85076224674
    Appears in Collections:[Chia-Huei Lee] Periodical Articles

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