RNA binding motif protein 3 (RBM3) drives radioresistance in nasopharyngeal carcinoma by reducing apoptosis via the PI3K/AKT/Bcl-2 signaling pathway

American Journal of Translational Research

Hua Yang¹  Rui Ma²  Li-Na Zhao³ 

[1] Department of Radiation Medicine, The Faculty of Preventive Medicine, Fourth Military Medical University, No. 169 Changle West Road 169, Xian 710032, China;Department of Radiation Oncology, Xijing Hospital, The Fourth Military Medical University, No. 127 West Changle Road, Xian 710032, China;Department of Thyroid-Breast-Vascular Surgery, Xijing Hospital, The Fourth Military Medical University, No. 127 West Changle Road, Xian 710032, China

关键词: RBM3;    nasopharyngeal carcinoma;    radioresistance;    apoptosis;    Bcl-2;    PI3K;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Radioresistance is an important obstacle to nasopharyngeal carcinoma (NPC) therapy. In this study, we explored the role of RNA-binding motif protein 3 (RBM3) in the radioresistance of NPC and its underlying mechanism. We measured the expression of RBM3 in 20 clinical NPC tissues and in NPC cell lines. We found that RBM3 was upregulated in radioresistant NPC tissues and cells. Radioresistant NPC cells (CNE1/IR) and parental NPC cells (CNE1) were subjected to RBM3-shRNA knockdown and RBM3 overexpression, respectively. RBM3 depletion in CNE1/IR cells sensitized cells to radiotherapy, increased DNA damage, and accelerated the rate of apoptosis. In contrast, RBM3 overexpression in CNE1 cells significantly enhanced radioresistance and reduced the rate of apoptosis. Additionally, radioresistance conferred by RBM3 was attributed to the activation of the AKT/Bcl-2 signaling pathway and reduction of caspase 3. Inhibition of AKT signaling attenuated RBM3-mediated radioresistance. Furthermore, RBM3 directly interacted with PI3K subunit p85 in NPC cell lines. Altogether, our data demonstrate that RBM3 enhances radioresistance by inhibiting the apoptotic response to radiotherapy through the PI3K/AKT/Bcl-2 signaling pathway. RBM3 may serve as a novel factor for predicting radioresistance and as a molecular target in the treatment of NPC.

【 授权许可】

CC BY-NC