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MiR-449a attenuates autophagy of T-cell lymphoma cells by downregulating ATG4B expression

  • Zhang, Nan (Department of Hematology, The General Hospital of Western Theater Command) ;
  • Qiu, Ling (Department of Hematology, The General Hospital of Western Theater Command) ;
  • Li, Tao (Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Army Medical University) ;
  • Wang, Xiao (Department of Hematology, The General Hospital of Western Theater Command) ;
  • Deng, Rui (Department of Hematology, The General Hospital of Western Theater Command) ;
  • Yi, Hai (Department of Hematology, The General Hospital of Western Theater Command) ;
  • Su, Yi (Department of Hematology, The General Hospital of Western Theater Command) ;
  • Fan, Fang-yi (Department of Hematology, The General Hospital of Western Theater Command)
  • Received : 2019.08.29
  • Accepted : 2019.11.05
  • Published : 2020.05.31

Abstract

Increasing evidence suggests the role of miR-449a in the regulation of tumorigenesis and autophagy. Autophagy plays an important role in the malignancy of T-cell lymphoma. However, it is still unknown whether miR-449a is associated with autophagy to regulate the malignancy of T-cell lymp homa. In this study, we for the first time demonstrated that miR-449a enhanced apoptosis of T-cell lymphoma cells by decreasing the degree of autophagy. Further, miR-449a downregulated autophagy-associated 4B (ATG4B) expression, which subsequently reduced the autophagy of T-cell lymphoma cells. Mechanistically, miR-449a decreased ATG4B protein level by binding to its mRNA 3'UTR, thus reducing the mRNA stability. In addition, studies with nude mice showed that miR-449a significantly inhibited lymphoma characteristics in vivo. In conclusion, our results demonstrated that the "miR-449a/ATG4B/autophagy" pathway played a vital role in the malignancy of T-cell lymphoma, suggesting a novel therapeutic target.

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