Knockdown of EBV-encoded circRNA circRPMS1 suppresses nasopharyngeal carcinoma cell proliferation and metastasis through sponging multiple miRNAs

Abstract

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.