EB病毒诱导OASL表达上调促进鼻咽癌发生发展的作用及机制研究

In this study, we found OASL (2'-5'-oligoadenylate synthase-like protein) was higher expressed in NPC (nasopharyngeal carcinoma) tissues and cell lines after RNA sequencing and bioinformatics analysis, which had been validated by real-time RT-PCR and western blot. And we found that mRNA and protein expression levels of interferon family proteins (IFNa/b) and their downstream OAS family proteins were increased in NPC cell lines after transient EBV infection. We also found overexpression of OASL could promote cell proliferation and colony formation in NPC cell lines. Inclusion, we hypothesize that infection of EBV in nasopharyngeal epithelial cells promotes the development of NPC through regulating interferon signaling pathway and upregulating OASL expression level..Our project will transient infect EBV in IFNa/b overexpression or knock down stable NPC cell lines, try to explore the relationships of EVB infection, IFN and OASL, to reveal the relevance and molecular mechanisms between the development of NPC and OASL expression. The project will explore the molecular mechanisms of OASL promote NPC progress through mass spectrometry, co-immunoprecipitation and other techniques, will find critical molecules of related signaling pathways to further clarify the downstream signaling pathways of OASL regulating NPC development, and provide new potential target for clinical treatments of NPC.

课题组通过对鼻咽癌肿瘤组织及细胞系进行RNA-seq分析及验证，发现2'-5'-寡聚腺苷酸合成酶样蛋白（OASL）在鼻咽癌组织及细胞系中高表达。同时发现EBV瞬时感染鼻咽癌细胞系能够诱导干扰素及其下游OAS家族表达水平上调，此外OASL稳定过表达能够促进鼻咽癌细胞增殖及克隆形成能力。我们推测EBV感染鼻咽上皮细胞通过调控干扰素信号通路上调OASL表达促进鼻咽癌的发生发展。本项目拟先在过表达或敲低干扰素的鼻咽癌细胞系中瞬时感染EBV，研究EBV感染与干扰素及OASL的关系、揭示OASL与鼻咽癌发生发展的相关性及分子机制；利用蛋白质谱、免疫共沉淀等技术明确OASL促进鼻咽癌发生发展的具体分子机制；利用real-time PCR及western blot等技术检测功能效应相关信号通路关键分子的表达情况，进一步明确OASL调控鼻咽癌发生发展的信号通路；为鼻咽癌临床治疗提供新的、有效的分子靶标。