人类基因组计划及其后续的DNA元件百科全书计划（The Encyclopedia of DNA Elements Project,ENCODE）研究成果表明,蛋白质编码基因序列仅占人类基因组序列的1%-3%,人基因组中绝大部分可转录的序列为长链非编码RNA（long non-coding RNA,lnc RNAs）[1].Lnc RNA广泛地存在于各种生物中,且随着生物复杂程度的升高,基因组中lnc RNA序列的比例也相应地增大,提示lnc RNA在生物进化过程中可能有着重要意义[2-4]。
Epstein-Barr virus(EBV)is associated with nasopharyngeal carcinoma(NPC)tumorigenesis.However,the mechanism(s)connecting EBV infection and NPC remain unclear.Recently,a new class of EBV microRNAs(miRNAs)has been described.To determine how EBV miRNAs control the expression of host genes,and to understand their potential role in NPC tumorigenesis,we profiled the expression of 44 mature EBV miRNAs and potential host genes in NPC and non-tumor nasopharyngeal epithelial tissues.We found that 40 EBV miRNAs from the BART transcript were highly expressed in NPC.Analysis of potential BART miRNA target genes revealed that 3140 genes and several important pathways might be involved in the carcinogenesis of NPC.A total of 105 genes with potential EBV miRNA binding sites were significantly downregulated,suggesting that EBV miRNAs may regulate these genes and contribute to NPC carcinogenesis.An EBV miRNA and host gene regulation network was generated to provide useful clues for validating of EBV miRNA functions in NPC tumorigenesis.
人类鼻咽黏膜表面的分泌物中富含天然免疫蛋白,腭、肺及鼻咽上皮克隆(palate,lung and nasal epithelium clone,PLUNC)蛋白家族成员SPLUNC1和LPLUNC1就是其中的重要组成部分,这两个蛋白在鼻咽上皮相对特异高表达,它们都具有杀菌/渗透增强蛋白(bactericidal/permeability-increasing protein,BPI)结构域,可通过BPI结构域与细菌脂多糖(lipopolysaccharides,LPS)结合从而直接杀灭或抑制细菌生长,也可以有效抑制EB病毒(Epstein-Barr virus,EBV)等致癌微生物对鼻咽上皮的侵袭从而发挥其免疫防御功能.它们还可以通过抑制IL-6等炎症因子的分泌和NF-κB、STAT3等炎症相关通路的激活,阻止鼻咽部的慢性炎症反应及鼻咽上皮的恶性转化.在鼻咽癌细胞中重新表达PLUNC蛋白,可以通过促分裂素原活化蛋白激酶(Mitogen-activated protein kinase,MAPK)或miR-141-PTEN-AKT等信号通路抑制鼻咽癌细胞的增殖,促进鼻咽癌细胞的凋亡.进一步深入研究PLUNC蛋白家族在鼻咽癌发病中的作用机制,对指导鼻咽癌的防治具有重要的意义.
