1. MiRNA-223-3p Affects Mantle Cell Lymphoma Development by Regulating the CHUK/NF-ƘB2 Signaling Pathway.
- Author
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Yuan, Jingjing, Zhang, Qing, Wu, Shengsheng, Yan, Suran, Zhao, Ran, Sun, Yajuan, Tian, Xiaoxu, and Zhou, Keshu
- Subjects
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MANTLE cell lymphoma , *LYMPHOMAS , *PROGNOSIS , *CELL proliferation , *WESTERN immunoblotting - Abstract
Background: Mantle cell lymphoma (MCL) is an aggressive malignancy that accounts for 5– 10% of non-Hodgkin's lymphoma. MiRNA-223-3p has been demonstrated to be down-regulated in MCL and is a useful prognostic factor. However, little is known about underlying molecular mechanism of miRNA-233-3p in MCL. Methods: The expression levels of miRNA-223-3p and CHUK mRNA in MCL cells were detected by real-time quantitative PCR (RT-qPCR). The effects of miRNA-223-3p/CHUK overexpression/knockdown on MCL cell proliferation and apoptosis were measured by CCK-8 assay and annexin V PE/7-AAD-based flow cytometry/TUNEL assay, respectively. A nude mouse subcutaneous xenograft model was used to further evaluate the potential effects in vivo. Dual-luciferase reporter assay was used to verify the inhibitory effect of miRNA-223-3p on CHUK. Furthermore, the regulatory function of miRNA-223-3p on the CHUK/NF-ƘB2 axis was assessed by RT-qPCR, western blot and immunofluorescence. Results: In the present study, miRNA-223-3p overexpression inhibited proliferation and accelerated apoptosis of MCL cells in vitro and in vivo. The results of Luciferase reporter assay showed that CHUK was a direct target of miRNA-223-3p in HEK293T cells. Furthermore, the results of RT-qPCR, western blot confirmed that CHUK was targeted and negatively regulated by miRNA-223-3p for repressing NF-ƘB2 pathway activation in MCL cells. Importantly, CHUK overexpression promoted proliferation and suppressed apoptosis of MCL cells, whereas CHUK knockdown reversed down-regulated miRNA-223-3p -accelerated cell proliferation in vitro. Conclusion: In conclusion, miRNA-223-3p affects MCL development by regulating the CHUK/NF-ƘB2 signaling pathway, which is crucial to provide a novel therapeutic strategy. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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