Dual Suppressive Effect of miR-34a on the FOXM1/eEF2-Kinase Axis Regulates Triple-Negative Breast Cancer Growth and Invasion

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Recep BayraktarBulent Ozpolat

Abstract

Purpose: Recent studies indicated that dysregulation of noncoding RNAs (ncRNA) such as miRNAs is involved in pathogenesis of various human cancers. However, the molecular mechanisms underlying miR-34a are not fully understood in triple-negative breast cancer (TNBC).Experimental Design: We performed in vitro functional assays on TNBC cell lines to investigate the role of miR-34a in FOXM1/eEF2K signaling axis. TNBC tumor xenograft models were used for in vivo therapeutic delivery of miR-34a.Results: In this study, we investigated the role of p53-driven ncRNA miR-34a and found that miR-34a is associated with significantly longer patient survival in TNBC and inversely correlated with levels of proto-oncogenic eEF2K, which was associated with significantly shorter overall patient survival. We showed that miR-34a directly binds to the 3'-untranslated region of eEF2K and FOXM1 mRNAs and suppresses their expression, leading to inhibition of TNBC cell proliferation, motility, and invasion. Notably, restoring miR-34a expression recapitulated the effects of inhibition of eEF2K and FOXM1, the transcription factor for eEF2K and the direct target of p53, in TNBC cell lines, whereas overexpression of eEF2K and FOXM1 rescued the effects and si...Continue Reading

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Citations

Mar 15, 2019·Endocrine-related Cancer·Feng WuZhaohui Mo
May 8, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Didem Karakas, Bulent Ozpolat
Mar 20, 2020·Molecular Cancer·Francesca CrudeleStefano Volinia
May 15, 2020·International Journal of Molecular Sciences·Sherien M El-DalyGeorge A Calin
Oct 12, 2018·Journal of Leukocyte Biology·Fadoua BelaibaAmel Benammar Elgaaïed
May 30, 2019·Frontiers in Immunology·Recep BayraktarGeorge A Calin
May 3, 2020·International Journal of Molecular Sciences·Yoshihisa TokumaruKazuaki Takabe
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May 11, 2019·Journal of Experimental & Clinical Cancer Research : CR·Guohui HuShiwen Luo
Jan 18, 2019·Molecular Therapy. Nucleic Acids·Hamada A MokhlisBulent Ozpolat
Feb 19, 2021·Life Sciences·Jie LiuChen-Yan Zhang
Apr 3, 2021·Journal for Immunotherapy of Cancer·Dong Ho ShinJuan Fueyo
Apr 17, 2021·ACS Pharmacology & Translational Science·Ferah Comert OnderBulent Ozpolat
May 8, 2021·Cancer Metastasis Reviews·Sijing LiLi Sun
Aug 6, 2021·Pathology, Research and Practice·Mingxia JiangChengxin Song
Feb 7, 2020·Journal of Chemical Information and Modeling·Ferah Comert OnderMehmet Ay
Nov 4, 2021·Cancer Immunology, Immunotherapy : CII·Bharat K R ChagantyZhen Fan
Dec 17, 2019·Molecular Therapy. Nucleic Acids·Xiaomin LiuZhongliang Ma

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