Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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LncRNA CRNDE Promotes the Progression of B-cell Precursor Acute Lymphoblastic Leukemia by Targeting the miR-345-5p/CREB Axis

  • Wang, Weimin (Department of Hematology, The First Affiliated Hospital of Zhengzhou University) ;
  • Wu, Feifei (Department of Hematology, The First Affiliated Hospital of Zhengzhou University) ;
  • Ma, Ping (Department of Hematology/Oncology, Children's Hospital Affiliated of Zhengzhou University) ;
  • Gan, Silin (Department of Hematology, The First Affiliated Hospital of Zhengzhou University) ;
  • Li, Xue (Department of Hematology, The First Affiliated Hospital of Zhengzhou University) ;
  • Chen, Li (Department of Hematology, The First Affiliated Hospital of Zhengzhou University) ;
  • Sun, Ling (Department of Hematology, The First Affiliated Hospital of Zhengzhou University) ;
  • Sun, Hui (Department of Hematology, The First Affiliated Hospital of Zhengzhou University) ;
  • Jiang, Zhongxing (Department of Hematology, The First Affiliated Hospital of Zhengzhou University) ;
  • Guo, Feng (Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University)
  • Received : 2020.03.12
  • Accepted : 2020.07.21
  • Published : 2020.08.31
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Abstract

The imbalance between the proliferation and apoptosis of B-cell precursors is an important contributor to the pathogenesis of B-cell precursor acute lymphoblastic leukemia (BCP-ALL), while its specific regulatory mechanism remains perplexing. This study aimed to expound the underlying mechanism of the proliferation and apoptosis of BCP-ALL cells from the perspective of non-coding RNA. In this study, long non-coding RNA colorectal neoplasia differentially expressed (LncRNA CRNDE) was upregulated in the bone marrow of BCP-ALL patients and BCP-ALL cell lines (NALM-6 and RS4;11). Functionally, LncRNA CRNDE knockdown restrained cell proliferation and boosted cell apoptosis in NALM-6 and RS4;11 cells. The subsequent investigation confirmed that LncRNA CRNDE bound to miR-345-5p and negatively regulated miR-345-5p expression. The overexpression of miR-345-5p suppressed cell proliferation and boosted cell apoptosis in NALM-6 and RS4;11 cells. Further experiments revealed that miR-345-5p downregulated cyclic AMP response element-binding protein (CREB) expression by targeting its mRNA directly. CREB overexpression reversed the effect of miR-345-5p mimic on cell proliferation and apoptosis in NALM-6 and RS4;11 cells. Finally, in vivo experiments showed that LncRNA CRNDE knockdown prolonged the survival of mice xenotransplanted with NALM-6 cells. In conclusion, LncRNA CRNDE upregulated CREB expression by suppressing miR-345-5p, thus promoting cell proliferation and reducing cell apoptosis in BCP-ALL.

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References

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