Article ; Online: MicroRNA, miR-501 regulate the V(D)J recombination in B cells.
2023 Volume 480, Issue 24, Page(s) 2061–2077
Abstract: ... responsible for V(D)J recombination, is important to prevent genomic rearrangements and ... assay. Importantly, overexpression of miRNAs led to inhibition of V(D)J recombination in B cells ... and thus V(D)J recombination and its possible implications on immunoglobulin leukemogenesis. ...
Abstract | The stringent regulation of RAGs (Recombination activating genes), the site-specific endonuclease responsible for V(D)J recombination, is important to prevent genomic rearrangements and chromosomal translocations in lymphoid cells. In the present study, we identify a microRNA, miR-501, which can regulate the expression of RAG1 in lymphoid cells. Overexpression of the pre-miRNA construct led to the generation of mature miRNAs and a concomitant reduction in RAG1 expression, whereas inhibition using anti-miRs resulted in its enhanced expression. The direct interaction of the 3'UTR of miR-501 with RAG1 was confirmed by the reporter assay. Importantly, overexpression of miRNAs led to inhibition of V(D)J recombination in B cells, revealing their impact on the physiological function of RAGs. Of interest is the inverse correlation observed for miR-501 with RAG1 in various leukemia patients and lymphoid cell lines, suggesting its possible use in cancer therapy. Thus, our results reveal the regulation of RAG1 by miR-501-3p in B cells and thus V(D)J recombination and its possible implications on immunoglobulin leukemogenesis. |
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MeSH term(s) | Humans ; V(D)J Recombination/genetics ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; MicroRNAs/genetics ; B-Lymphocytes |
Chemical Substances | Homeodomain Proteins ; MicroRNAs ; MIRN501 microRNA, human |
Language | English |
Publishing date | 2023-10-29 |
Publishing country | England |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 2969-5 |
ISSN | 1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021 |
ISSN (online) | 1470-8728 |
ISSN | 0006-2936 ; 0306-3275 ; 0264-6021 |
DOI | 10.1042/BCJ20230250 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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