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KMID : 0578320200430080718
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Molecules and Cells
2020 Volume.43 No. 8 p.718 ~ p.727
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LncRNA CRNDE Promotes the Progression of B-cell Precursor Acute Lymphoblastic Leukemia by Targeting the miR-345-5p/CREB Axis
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Wang Weimin
Wu Feifei
Ma Ping
Gan Silin
Li Xue
Chen Li
Sun Ling
Sun Hui
Jiang Zhongxing
Guo Feng
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Abstract
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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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KEYWORD
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B-cell precursor acute lymphoblastic leukemia, cyclic AMP-binding protein, long non-coding RNA colorectal neoplasia differentially expressed, miR-345-5p
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