STAT3信号通路激活促进了肿瘤增殖、侵袭和血管生成等恶性生物学行为；病毒癌基因LMP1能激活STAT3信号通路并促进鼻咽癌的恶性进展。miRNA是基因表达调控网络的重要一员。我们前期发现在鼻咽癌中LMP1能上调miR-19b，进而靶向抑制STAT3的抑制因子SOCS1的表达；由此推测LMP1/miR-19b/SOCS1是STAT3激活的新分子旁路。为阐明该分子旁路在鼻咽癌进展中的作用及机制，本课题拟通过体内细胞、体外裸鼠移植瘤模型，过表达或敲低该通路中的两个关键节点LMP1和miR-19b，检测SOCS1及pSTAT3的表达，阐明其对STAT3信号通路的影响；qPCR芯片等技术检测相关效应分子，并同时检测增殖、侵袭和血管生成等恶性生物学行为，阐明该分子通路的生物学行为的效应；并在前期基础上进一步扩大人鼻咽癌组织标本，验证上述相关分子表达及与临床病理参数的关系；以期获得鼻咽癌治疗的新靶标。

Activated STAT3 signaling is involved in progession of malignancy by promoting proliferation, invasion and angiogenesis. Virus oncogene latent membrane protein 1 (LMP1) induce a constitutively activated STAT signaling, then promote malignant progress in nasopharyngeal carcinoma (NPC). miRNA is key member in the regulation network of gene exprssion. Actually, we previously found miR-19b upregulated by LMP1 in NPC. Moreover, miR-19b targetedly inhibit of SOCS1, a key inhibitor of STAT3 signaling. In view of this, we put forward the hypothesis that there is a bypass of STAT3 signaling, LMP1/miR-19b/SOCS1/STAT3. To elucidate the molecular mechanism of the bypass and it’s role in NPC progression, we plan to 1) intervene the key nodes, LMP1 and miR-19b, of the bypass signaling through overexprssion and knockdown in vitro and in vivo; detect the expression of downstream nodes, SOCS1 and phosphated STAT3; Detect the associated effector moleculars by qPCR array and other molecular boilogy technics, and detect the resulting biological effections such as proliferation, invasion and angiogensis in NPC. 2) Verify the change of above molecules in tissue of NPC and chronic inflammated nasopharygeal epithelia, and the clinicopatholgical parameters were analysised. Expected results will provide new molecular targets for therapy of NPC.