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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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MicroRNA-301b promotes cell proliferation and apoptosis resistance in triple-negative breast cancer by targeting CYLD

  • Song, Hongming (Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University) ;
  • Li, Dengfeng (Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University) ;
  • Wu, Tianqi (Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University) ;
  • Xie, Dan (Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University) ;
  • Hua, Kaiyao (Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University) ;
  • Hu, Jiashu (Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University) ;
  • Deng, Xiaochong (Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University) ;
  • Ji, Changle (Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University) ;
  • Deng, Yijun (Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University) ;
  • Fang, Lin (Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University)
  • Received : 2018.07.22
  • Accepted : 2018.09.27
  • Published : 2018.11.30
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Abstract

Aberrant expression of microRNAs (miRNAs) plays important roles in carcinogenesis and tumor progression. However, the expression and biological role of miR-301b in triple-negative breast cancer (TNBC) remains unclear. Here we aimed to evaluate the roles and mechanisms of miR-301b in TNBC cells. miR-301b expression was assessed in TNBC specimens and cell lines by quantitative Real-Time PCR (qRT-PCR). TNBC cells were transfected with miR-301b mimics, inhibitors or Cylindromatosis (CYLD) small interfering RNA (siRNA) using Lipofectamine 2000. The functional roles of miR-301b were determined by cell proliferation, colony formation, and apoptosis assays. Western blots and qRT-PCR were used to measure the expression of mRNAs and proteins in the cells. We found that miR-301b was upregulated in TNBC specimens and cell lines. Overexpression of miR-301b promoted cell proliferation in TNBC cells, while inhibited the apoptosis induced by 5-FU. CYLD was downregulated by miR-301b at both mRNA and protein levels in TNBC cells. Dual-luciferase report assay confirmed that miR-301b downregulated CYLD by direct interaction with the 3'-untranslated region(3'-UTR) of CYLD mRNA. $NF-{\kappa}B$ activation was mechanistically associated with miR-301b-mediated downregulation of CYLD. However, inhibition of miR-301b reversed all the effects of miR-301b. In conclusion, miR-301b plays an oncogenic role in TNBC possibly by downregulating CYLD and subsequently activating $NF-{\kappa}B$ p65, and this may provide a novel therapeutic approach for TNBC.

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References

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