Table3_Competitive Endogenous RNA Landscape in Epstein-Barr Virus Associated Nasopharyngeal Carcinoma.XLSX

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.

已有研究证实，非编码RNA（non-coding RNAs）可发挥关键调控功能，尤其在肿瘤发生发展进程中。本研究通过构建环状RNA（circular RNAs, circRNA）-微小RNA（microRNAs, miRNA）-信使RNA（messenger RNAs, mRNA）共表达网络，并对信使RNA、微小RNA及环状RNA开展差异表达分析，探究了二者在鼻咽癌（Nasopharyngeal Carcinoma, NPC）中的调控作用。具体而言，EB病毒（Epstein-Barr virus, EBV）感染已被认定为鼻咽癌的重要危险因素，且EBV阳性（EBV+）与EBV阴性（EBV-）的鼻咽癌亚型可能存在潜在病理学差异。本研究通过比对永生化非癌鼻咽上皮细胞系与鼻咽癌细胞系的表达谱，在三组比较维度下筛选得到差异表达的编码RNA与非编码RNA：癌组织与非癌组织、EBV+与EBV-鼻咽癌、转移性与非转移性鼻咽癌。研究团队依托共表达分析与微小RNA靶标预测工具，构建了由信使RNA、微小RNA及环状RNA组成的内源竞争RNA（competing endogenous RNA, ceRNA）网络，并在该网络中鉴定出CDKN1B、ZNF302、ZNF268及RPGR的调控性内源竞争RNA轴。上述差异表达调控轴，结合本研究分析得到的其余微小RNA-环状RNA对，有助于阐明鼻咽癌进展核心的遗传与表观遗传改变，以及EBV阳性与阴性鼻咽癌亚型间的差异。