EB病毒LMP1介导鼻咽癌miR-487b-IRS1通路轴的机制研究

Nasopharyngeal carcinoma (NPC) is an important type of head and neck cancer in southern China, with low differentiation of pathological and high metastasis clinical features. Recent studies showed that the process of epithelial-mesenchymal transition (EMT) and cancer stemless was involved in the metastasis. Epstein-Barr Virus (EBV) as the first confirmed DNA tumor virus, encodes a vital protein called latent membrane protein 1 (LMP1), which plays a key role in the pathogenesis of nasopharyngeal carcinoma. Our pervious study found that LMP1 as an important driven gene, increased miR-487b expression, and specific targeting insulin receptor substrate-1 (IRS1) in promoting EMT process and stemness by inhibiting E-cadherin, and upregulating Vimentin expression, which involved in cell migration and invasion. Based on previous results, we will use Western Blot, Transwell assays, animal models, immunohistochemistry, clinical survial analyze and cancer stemness biomarker detection to elucidate the molecular mechanism of EBV encoded LMP1 mediated EMT process and stemness by miR-487b-IRS1 axis in NPC, which will provide new mechanism for virus carcinogenesis research.

鼻咽癌是我国南方地区高发的一类重要的头颈部肿瘤，以低分化和高转移为主要的临床病理特征。新近研究发现，上皮-间质转化（EMT）与肿瘤干性参与肿瘤转移过程。Epstein-Barr Virus（EBV）作为首个被证实的DNA致瘤病毒，其编码的潜伏膜蛋白1（LMP1）在鼻咽癌的发病过程中起着关键作用。研究者前期工作发现，LMP1作为重要的驱动基因，可以上调miR-487b的表达，并通过靶向胰岛素受体底物1（IRS1），抑制E-cadherin，上调Vimentin的表达，促进细胞上皮-间质转化及肿瘤干性，参与细胞的侵袭和转移。申请者拟以鼻咽癌为模型，通过Western Blot、Transwell、动物实验、免疫组化、临床生存分析及肿瘤干细胞标志物检测等实验，阐明EB病毒编码的LMP1通过miR-487b-IRS1轴参与上皮-间质转化和肿瘤干性调节的分子机制，为病毒致瘤研究提供新机制。

鼻咽癌是我国南方地区高发的一类重要的头颈部肿瘤，以低分化和高转移为主要的临床病理特征。新近研究发现，上皮-间质转化（EMT）与肿瘤干性参与肿瘤转移过程。Epstein-Barr Virus（EBV）作为首个被证实的DNA致瘤病毒，其编码的潜伏膜蛋白1（LMP1）在鼻咽癌的发病过程中起着关键作用。本研究以鼻咽癌为模型，通过Western Blot、Transwell、动物实验、免疫组化、临床生存分析及肿瘤干细胞标志物检测等实验，发现LMP1作为重要的驱动基因，可以上调miR-487b的表达，并通过靶向胰岛素受体底物1（IRS1），抑制E-cadherin，上调Vimentin的表达，促进细胞上皮-间质转化及肿瘤干性，参与细胞的侵袭和转移。本研究阐明了EB病毒编码的LMP1通过miR-487b-IRS1轴参与上皮-间质转化和肿瘤干性调节的分子机制，为病毒致瘤研究提供新机制。