Shuai He
Ya-Qing Zhou
Chu-Jun Liu
Shu-Qiang Liu
Wan Peng
Yu-Xiang Liu
Pan-Pan Wei
Jin-Xin Bei
Chun-Ling Luo
a Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, PR China;
b Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China;
c Department of Medical Oncology, National Cancer Centre of Singapore, Singapore 169610, Singapore
Funds: This work was supported by the National Natural Science Foundation of China (81802711), the China Postdoctoral Science Foundation (2019T120781, 2018M631032, and 2017M622882), the Sci-Tech Project Foundation of Guangzhou City (201707020039), Guangdong Innovative and Entrepreneurial Research Team Program (2016ZT06S638), the National Science Foundation for Excellent Young Scholars (81222035), Special Support Program of Guangdong (BJX), Chang Jiang Scholars Program (BJX), Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education (202101). We thank all the participants in the study and staff at the biobank of SYSUCC for processing sample preparation and staffs at the High-Throughput Analysis Platform (HTAP) of SYSUCC for data generation and processing.
Received Date: 2021-03-15
Accepted Date:2021-05-01
Rev Recd Date:2021-04-29
Publish Date:2021-07-20
Abstract
Abstract
RNA binding motif proteins (RBMs) have been widely implicated in the tumorigenesis of multiple human cancers but scarcely studied in nasopharyngeal carcinoma (NPC). Here, we compare the mRNA levels of 29 RBMs between 87 NPC and 10 control samples. We find that RBM47 is frequently upregulated in NPC specimens, and its high expression is associated with the poor prognosis of patients with NPC. Biological experiments show that RBM47 plays an oncogenic role in NPC cells. Mechanically, RBM47 binds to the promoter and regulates the transcription of BCAT1, and its overexpression partially rescues the inhibitory effects of RBM47-knockdown on NPC cells. Moreover, transcriptome analysis reveals that RBM47 regulates alternative splicing of pre-mRNA, including those cancer-related, to a large extent in NPC cells. Furthermore, RBM47 binds to hnRNPM and cooperatively regulates multiple splicing events in NPC cells. In addition, we find that knockdown of hnRNPM inhibits proliferation and migration of NPC cells. Our study, taken together, shows that RBM47 promotes the progression of NPC through multiple pathways, acting as a transcriptional factor and a modulator of alternative splicing in cooperation with hnRNPM. Our study also highlights that RBM47 and hnRNPM could be prognostic factors and potential therapeutic targets for NPC.Keywords: RBM47,
BCAT1,
Alternative splicing,
hnRNPM,
Nasopharyngeal carcinoma (NPC)
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