國家衛生研究院 NHRI:Item 3990099045/10008
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    題名: MiR-182 promotes proliferation and invasion and elevates the HIF-1alpha-VEGF-A axis in breast cancer cells by targeting FBXW7
    其他題名: MiR-182 promotes proliferation and invasion and elevates the HIF-1α-VEGF-A axis in breast cancer cells by targeting FBXW7
    作者: Chiang, CH;Chu, PY;Hou, MF;Hung, WC
    貢獻者: National Institute of Cancer Research
    摘要: The feature of imperfect complementary effect of miRNAs to mRNAs implies that miRNAs may simultaneously target different mRNAs to affect multiple aspects of tumorigenesis. In our previous results, we demonstrated that miR-182 was over-expressed in breast cancer cell lines and clinical tumor tissues and its up-regulation increased tumorigenicity and invasiveness by repressing a tumor suppressor RECK. In this study, we showed that overexpression miR-182 regulated actin distribution and filopodia formation to increase invasiveness of breast cancer cells. In addition, miR-182 enhanced cell cycle progression and proliferation. We further identified the E3 ubiquitin-protein ligase FBXW7 as a target gene of miR-182. We also demonstrated that miR-182-overexpressing cells were highly sensitive to hypoxia. Under hypoxic condition, HIF-1alpha and VEGF-A proteins were significantly upregulated in these cells. In addition, the conditioned medium of miR-182-overexpressing cells contained more VEGF-A than the control cells and induced angiogenesis more efficiently in vitro. All these effects could be counteracted by ectopic expression of FBXW7 in cells or neutralization of VEGF-A in the conditioned media by specific antibody. Finally, our data showed that miR-182 expression was inversely correlated with FBXW7 in breast tumor tissues. In conclusion, our study explores a novel mechanism by which miR-182 elevates HIF-1alpha expression to promote breast cancer progression.
    日期: 2016-09
    關聯: American Journal of Cancer Research. 2016 Sep;6(8):1785-1798.
    Link to: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004079/
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2156-6976&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000383369900015
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85000751813
    顯示於類別:[洪文俊] 期刊論文

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