Wan Xun-Xun, Yi Hong, Qu Jia-Quan, He Qiu-Yan, Xiao Zhi-Qiang
Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Oncol Rep. 2015 Nov;34(5):2585-601. doi: 10.3892/or.2015.4237. Epub 2015 Sep 1.
Nasopharyngeal carcinoma (NPC) is commonly diagnosed in southern Asia. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally. Increasing evidence suggests that the dysregulation of miRNAs promotes NPC tumorigenesis. Epstein-Barr virus (EBV) infection and EBV-encoded miRNAs are also associated with the development of NPC. However, it is unclear how cellular and EBV miRNAs jointly regulate target genes and signaling pathways in NPC. In the present study, we analyzed the differential cellular and EBV miRNA expression profiles in 20 pooled NPC tissues using microarrays. We found that 19 cellular miRNAs and 9 EBV miRNAs were upregulated and 31 cellular miRNAs were downregulated in NPC tissues. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the 19 upregulated miRNAs target mainly the p53 signaling pathway in cancer, whereas the downregulated miRNAs regulate pathways related to cancer, focal adhesion and Erb, and MAPK signaling. In contrast, the upregulated EBV miRNAs target primarily the TGF-β and Wnt signaling pathways. Data also suggested that cellular miR-34b, miR-34c, miR-18a, miR‑200a/b, miR-449a, miR-31 and let-7 may be dysregulated in NPCs, and that the aberrant activation of their target genes in the p53 pathway and cell cycle enhance NPC cell survival and proliferation. In addition, EBV-miRNAs such as BART3 and BART5 target genes in the p53, TGF-β and Wnt signaling pathways to modulate NPC apoptosis and transformation. To better elucidate the interaction between miRNAs and target genes, we constructed an anti-correlated cellular and EBV miRNA/target gene regulatory network. The current findings may help dissect the roles played by cellular and EBV miRNAs during NPC tumorigenesis, and also provide useful biomarkers for the diagnosis and treatment of NPCs.
鼻咽癌（NPC）在南亚地区较为常见。微小RNA（miRNA）是一类小的非编码RNA，可在转录后水平调节基因表达。越来越多的证据表明，miRNA失调会促进鼻咽癌的发生。爱泼斯坦-巴尔病毒（EBV）感染及EBV编码的miRNA也与鼻咽癌的发生有关。然而，尚不清楚细胞miRNA和EBV miRNA如何共同调节鼻咽癌中的靶基因和信号通路。在本研究中，我们使用微阵列分析了20份合并的鼻咽癌组织中细胞miRNA和EBV miRNA的差异表达谱。我们发现，鼻咽癌组织中有19种细胞miRNA和9种EBV miRNA上调，31种细胞miRNA下调。基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析表明，上调的19种miRNA主要靶向癌症中的p53信号通路，而下调的miRNA则调节与癌症、粘着斑、Erb和丝裂原活化蛋白激酶（MAPK）信号相关的通路。相比之下，上调的EBV miRNA主要靶向转化生长因子-β（TGF-β）和Wnt信号通路。数据还表明，细胞miR-34b、miR-34c、miR-18a、miR-200a/b、miR-449a、miR-31和let-7在鼻咽癌中可能失调，并且它们在p53通路和细胞周期中的靶基因异常激活会增强鼻咽癌细胞的存活和增殖。此外，EBV-miRNA如BART3和BART5靶向p53、TGF-β和Wnt信号通路中的基因，以调节鼻咽癌的凋亡和转化。为了更好地阐明miRNA与靶基因之间的相互作用，我们构建了一个反相关的细胞和EBV miRNA/靶基因调控网络。目前的研究结果可能有助于剖析细胞miRNA和EBV miRNA在鼻咽癌发生过程中所起的作用，也为鼻咽癌的诊断和治疗提供有用的生物标志物。
