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miR-582 Suppresses the Proliferation of B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) Cells and Protects Them From Natural Killer Cell-Mediated Cytotoxicity.
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- Author(s): Li, Xinxin; Zhang, Yufei; He, Fei; Gao, Dan; Che, Bo; Cao, Xiuli; Huang, Siyong; Zheng, Minhua; Han, Hua
- Source:
Frontiers in Immunology; 4/20/2022, Vol. 13, p1-12, 12p- Subject Terms:
- Source:
- Additional Information
- Abstract: B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a malignancy characterized by the aberrant accumulation of immature B-cell precursors in bone marrow and other lymphoid organs. Although several intrinsic regulatory signals participating in BCP-ALL have been clarified, detailed intrinsic and extrinsic mechanisms that regulate BCP-ALL progression have not been fully understood. In the current study, we report that miR-582 is downregulated in BCP-ALL cells compared with normal B cells. Forced overexpression of miR-582 attenuated BCP-ALL cell proliferation and survival. We found that miR-582 overexpression disturbed the mitochondrial metabolism of BCP-ALL cells, leading to less ATP but more ROS production. Mechanistically, we identified PPTC7 as a direct target of miR-582. MiR-582 overexpression inhibited the activity of CoQ10, which is downstream of PPTC7 and played an important positive regulatory role in mitochondrial electron transportation. Finally, we found that overexpression of miR-582 upregulated the expression of immune checkpoint molecule CD276 and reduced NK cell-mediated cytotoxicity against BCP-ALL cells. CD276 blockade significantly increased NK cell-mediated cytotoxicity against miR-582-overexpressing BCP-ALL cells. Together, our research demonstrates that miR-582 acts as a negative regulator of BCP-ALL cells by reducing proliferation and survival, but protects BCP-ALL cells from NK cell-mediated cytotoxicity, suggesting that miR-582 may be a new therapeutic biomarker for BCP-ALL with CD276 blocker. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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