Competitive Endogenous RNA Landscape in Epstein-Barr Virus Associated Nasopharyngeal Carcinoma.

Xiandong Lin,Xiandong Lin,Keyu Lin,Tao Huang,Tao Huang,Jingfeng Zong,Jingfeng Zong,Ying Su,Ying Su,Steven Wang,Qianlan Zheng

doi:10.3389/fcell.2021.782473

Abstract

Non-coding RNAs have been shown to play important regulatory roles, notably in cancer development. In this study, we investigated the role of microRNAs and circular RNAs in Nasopharyngeal Carcinoma (NPC) by constructing a circRNA-miRNA-mRNA co-expression network and performing differential expression analysis on mRNAs, miRNAs, and circRNAs. Specifically, the Epstein-Barr virus (EBV) infection has been found to be an important risk factor for NPC, and potential pathological differences may exist for EBV+ and EBV- subtypes of NPC. By comparing the expression profile of non-cancerous immortalized nasopharyngeal epithelial cell line and NPC cell lines, we identified differentially expressed coding and non-coding RNAs across three groups of comparison: cancer vs. non-cancer, EBV+ vs. EBV- NPC, and metastatic vs. non-metastatic NPC. We constructed a ceRNA network composed of mRNAs, miRNAs, and circRNAs, leveraging co-expression and miRNA target prediction tools. Within the network, we identified the regulatory ceRNAs of CDKN1B, ZNF302, ZNF268, and RPGR. These differentially expressed axis, along with other miRNA-circRNA pairs we identified through our analysis, helps elucidate the genetic and epigenetic changes central to NPC progression, and the differences between EBV+ and EBV- NPC.

Highlights

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) associated malignancy with a characteristic geographical distribution
We identified axes of circRNA-miRNA-mRNA that are differentially expressed in each group of comparison
In the cancer vs. non-cancer and EBV+ vs EBV- differential expression (DE) comparisons, where more than one set of DE analysis was performed, we focused on the intersecting differentially expressed mRNAs, miRNAs, circRNAs (DEmRNAs, DE-miRNAs, DE-circRNAs)

Summary

Introduction

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) associated malignancy with a characteristic geographical distribution. NPC is a rare condition, with less than one case per 100,000 people per year. The occurrence of NPC is much more common among the populations in Southern China and Southeast Asia, with up to 25–50 cases per 100,000 people per year (Jain et al, 2016). Ethnic Chinese born in North America develop NPC less frequently compared to those in Southern China, implying that both genetic susceptibility and environmental factors contribute to the development of NPC (Buell, 1974). Ample evidence shown that infection of EBV is a risk factor for NPC (Tsao et al, 2017; Chan et al, 2018). EBV genome and gene products are detected in virtually all tumors in NPC-endemic areas.

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Discussion

Conclusion