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MicroRNA-148b 通过靶向 Bcl-w 促进细胞凋亡增强 B 细胞淋巴瘤细胞的放射敏感性。

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

机构信息

Department of Orthopaedics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.

Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.

出版信息

Int J Biol Sci. 2020 Jan 23;16(6):935-946. doi: 10.7150/ijbs.40756. eCollection 2020.

DOI:10.7150/ijbs.40756
PMID:32140063
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7053334/
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.

摘要

淋巴瘤是一种造血系统的恶性疾病，通常影响 B 细胞。miR-148b 的上调与 B 细胞淋巴瘤 (BCL) 的放射增敏作用有关。本研究旨在探讨 miR-148b 在调节 BCL 细胞放射敏感性中的作用及其潜在机制。miR-148b 可直接靶向 Bcl-w，降低照射后 BCL 细胞的活力和集落形成能力，同时促进细胞凋亡。这些变化伴随着线粒体膜电位降低、细胞色素 C 释放增加、切割的 caspase 9 和 caspase 3 水平升高，以及与线粒体凋亡途径相关的其他蛋白表达增加。Bcl-w 可有效抑制 miR-148b 的这些作用。此外，miR-148b 抑制了用照射 Raji 细胞异种移植物植入的裸鼠肿瘤的生长。在 BCL 患者中，miR-148b 水平下调，而 Bcl-w 水平上调；证实了 miR-148b 水平与 Bcl-w 水平之间存在显著的负相关。综上所述，这些实验表明，miR-148b 通过靶向抗凋亡 Bcl-w 促进了 BCL 细胞的辐射诱导凋亡。miR-148b 可能作为预测 BCL 放射敏感性的标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc72/7053334/dbe89deeab21/ijbsv16p0935g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc72/7053334/dbe89deeab21/ijbsv16p0935g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc72/7053334/20ed3c456866/ijbsv16p0935g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc72/7053334/682a41634117/ijbsv16p0935g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc72/7053334/46b4084a2c31/ijbsv16p0935g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc72/7053334/a0f5a1f4322a/ijbsv16p0935g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc72/7053334/87650645fa0c/ijbsv16p0935g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc72/7053334/fd62e164ce1e/ijbsv16p0935g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc72/7053334/dbe89deeab21/ijbsv16p0935g009.jpg

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