LncRNA CRNDE Promotes the Progression of B-cell Precursor Acute Lymphoblastic Leukemia by Targeting the miR-345-5p/CREB Axis

• Published in: Molecules and cells Vol. 43; no. 8; pp. 718 - 727
• Main Authors: Wang, Weimin, Wu, Feifei, Ma, Ping, Gan, Silin, Li, Xue, Chen, Li, Sun, Ling, Sun, Hui, Jiang, Zhongxing, Guo, Feng
• Format: Journal Article
• Language: Korean
• Published: 2020
• Subjects: B-cell precursor acute lymphoblastic leukemia; miR-345-5p; cyclic AMP-binding protein; long non-coding RNA colorectal neoplasia differentially expressed
• ISSN: 1016-8478; 0219-1032

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.