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敲除 EBV 编码的 circRNA circRPMS1 可通过多种 miRNA 的海绵化来抑制鼻咽癌细胞的增殖和转移
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
DOI https://doi.org/10.2147/CMAR.S218967
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 2
Editor who approved publication: Dr Teng
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