Int J Biol Sci 2020; 16(6):935-946. doi:10.7150/ijbs.40756

Research Paper

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

Si-hong Liu1,6,#, Pei-pei Wang2,6,#, Cun-te Chen3,6, Dan Li2,6, Qiong-yao Liu2,6, Lin Lv2,6, Xia Liu2,6, Li-na Wang2,6, Bao-xiu Li2,6, Cheng-yin Weng2,6, Xi-sheng Fang2,6, Xiao-fei Cao2,6, Hai-bo Mao2,6, Xiao-jun Chen2,6, Shao-li Luo4,6, Shu-xiang Zheng5,6, Guo-long Liu2,6,✉, Yong Wu2,6,✉

1. Department of Orthopaedics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
2. Department of Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
3. Department of Hematology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
4. Department of Gerontology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
5. Department of Obstetrics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
6. Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
#These authors contributed equally to this work.

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Citation:
Liu Sh, Wang Pp, Chen Ct, Li D, Liu Qy, Lv L, Liu X, Wang Ln, Li Bx, Weng Cy, Fang Xs, Cao Xf, Mao Hb, Chen Xj, Luo Sl, Zheng Sx, Liu Gl, Wu Y. MicroRNA-148b enhances the radiosensitivity of B-cell lymphoma cells by targeting Bcl-w to promote apoptosis. Int J Biol Sci 2020; 16(6):935-946. doi:10.7150/ijbs.40756. Available from http://www.ijbs.com/v16p0935.htm

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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.

Keywords: miR-148b, radiosensitivity, B-cell lymphoma, Bcl-w, apoptosis