MicroRNA-148b enhances the radiosensitivity of B-cell lymphoma cells by targeting Bcl-w to promote apoptosis.

ABSTRACT

Lymphoma is a malignant disease of the hematopoietic system that typically affects B cells. The up-regulation of miR-148b is associated with radiosensitization in B-cell lymphoma (BCL). This study aimed to explore the role of miR-148b in regulating the radiosensitivity of BCL cells and to investigate the underlying mechanism. miR-148b directly targeted Bcl-w, decreased the cell viability and colony formation, while promoted apoptosis, in irradiated BCL cells. These changes were accompanied by decreased mitochondrial membrane potential, release of cytochrome C, increased levels of the cleaved caspase 9 and caspase 3, and increased expression of other proteins related to the mitochondrial apoptosis pathway. These effects of miR-148b were effectively inhibited by Bcl-w. In addition, miR-148b inhibited the growth of tumors in nude mice implanted with xenografts of irradiated Raji cells. In patients with BCL, levels of miR-148b were downregulated, while levels of Bcl-w were upregulated; a significant negative correlation between levels of miR-148b and Bcl-w was confirmed. Taken together, these experiments showed that miR-148b promoted radiation-induced apoptosis in BCL cells by targeting anti-apoptotic Bcl-w. miR-148b might be used as a marker to predict the radiosensitivity of BCL.