Down-regulated miR-148b increases resistance to CHOP in diffuse large B-cell lymphoma cells by rescuing Ezrin - 25/08/18
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Highlights |
• | HDAC6 inhibits miR-148b expression via decreasing acetylation of histones H3/H4. |
• | Down-regulated miR-148b encourages CHOP resistance of DLBCL cells. |
• | Ezrin is a target of miR-148b. |
• | MiR-148b sensitizes CRL2631 cells to CHOP by targeting Ezrin. |
Abstract |
Background |
Aberrant microRNA (miRNAs) have recently been proposed as important regulators in acquiring resistance to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in diffuse large B-cell lymphoma (DLBCL). The purpose of this study was to establish the role of miR-148b in the development of CHOP resistance in DLBCL.
Methods |
The expression patterns of miR-148b, HDAC6, and Ezrin were detected in CHOP-resistant clinical specimens and a DLBCL cell line. miR-148b, HDAC6, and Ezrin in DLBCL cells were manipulated by cell transfection to explore the functional correlation between them. Cell viability was determined using a CCK-8 assay.
Results |
We found that miR-148b levels were markedly reduced and that the protein expressions of HDAC6 and Ezrin were increased in DLBCL CHOP-resistant clinical specimens and the cell line CRL2631/CHOP. Indeed, HDAC6 decreased the acetylation of histones H3 and H4 in the miR-148b promoter to inhibit miR-148b expression in DLBCL. Moreover, down-regulated miR-148b encouraged CHOP resistance in CRL2631 cells and miR-148b sensitized CRL2631 cells. We further revealed that Ezrin was negatively regulated by miR-148b and that the knockdown of Ezrin significantly attenuated CHOP resistance in CRL2631 cells induced by miR-148b silencing. MiR-148b also sensitized CRL2631/CHOP cell xenografts to CHOP in mice.
Conclusion |
Our data indicated that the high level of HDAC6 inhibited miR-148b via maintaining the low acetylation of histones H3 and H4 in the miR-148b promoter, thus rescuing Ezrin expression and promoting CHOP resistance in DLBCL.
Le texte complet de cet article est disponible en PDF.Keywords : DLBCL, CHOP resistance, MiR-148b, Ezrin, HDAC6
Plan
Vol 106
P. 267-274 - octobre 2018 Retour au numéro
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