Knockdown of EBV-encoded circRNA circRPMS1 suppresses nasopharyngeal carcinoma cell proliferation and metastasis through sponging multiple miRNAs
Authors Liu Q, Shuai M, Xia Y
Received 10 June 2019
Accepted for publication 30 July 2019
Published 27 August 2019 Volume 2019:11 Pages 8023—8031
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Yong Teng
Qianwen Liu,1 Mingxia Shuai,2 Yong Xia3
1Colorectal Anal Surgical Department, Hepatobiliary and Enteric Surgery Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China; 2Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China; 3Department of Blood Transfusion, Affiliated Hospital of Xiangnan University, Chenzhou, People’s Republic of China
Correspondence: Mingxia Shuai
Department of Otorhinolaryngology Head & Neck Surgery, Xiangya Hospital, Central South University, Xiangya Road No. 87, Changsha 410008, People’s Republic of China
Tel/fax +86 07 318 432 7332
Affiliated Hospital of Xiangnan University, West Renmin Road No. 25, Chenzhou 423000, People’s Republic of China
Tel/fax +86 0 735 222 3633
Background: Epstein-Barr virus (EBV)-produced non-coding RNAs, including circular RNA (circRNA), regulate host cell gene expression and play important roles in development of nasopharyngeal carcinoma (NPC). EBV-encoded circRNA circRPMS1 consists of the head-to-tail splicing of exons 2-4 from the RPMS1 gene. Its roles and mechanism on NPC remain unknown.
Purpose: In this study, we investigated the biological functions and molecular mechanisms of circRPMS1 in tumor proliferation, apoptosis, invasion, metastasis and as a potential biomarker for NPC diagnosis and prognosis.
Patients and methods: NPC tissues and the adjacent tissues were collected. Cell proliferation assay, cell apoptosis assay, cell invasion assay, luciferase reporter assay, RNA immunoprecipitation and tumor xenograft in nude mice were performed to analyze the circRPMS1 functions.
Results: We found that EBV-encoded circRPMS1 was increased in metastatic NPC and was associated with short survival time. Knockdown of circRPMS1 inhibited cell proliferation, induced apoptosis and repressed cell invasion in EBV-positive NPC cells. Further mechanism investigation revealed that circRPMS1-meadiated NPC oncogenesis through sponging multiple miRNA and promoting epithelial-mesenchymal transition (EMT). The inhibitors of miR-203, miR-31 and miR-451 could reverse the effects of circRPMS1 knockdown on NPC cells.
Conclusion: The findings indicate circRPMS1 as a potential therapeutic target for EBV-associated NPC. Our findings provide important understanding for the further elucidation on the therapeutic use of circRNA in NPC.
Keywords: Epstein–Barr virus, circular RNA, nasopharyngeal carcinoma, miRNA, epithelial-mesenchymal transition
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