淋巴细胞特异性转录因子SpiB在小细胞肺癌中的功能和调控研究

项目名称： 淋巴细胞特异性转录因子SpiB在小细胞肺癌中的功能和调控研究

项目编号： No.81502538

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 杜玮

作者单位： 天津医科大学

项目金额： 18.5万元

中文摘要： 与非小细胞肺癌相比，小细胞肺癌转移快，恶性程度高。利用RNA-Seq我们发现小细胞肺癌细胞表达一系列生理状态下仅表达于造血细胞中的转录因子包括SpiB。在不表达SpiB的鼠肺癌细胞LLC1中导入该蛋白之后进行小鼠皮下注射，其肺转移能力较对照组显著增强，并能上调MMP9、PLGF等肿瘤侵袭相关基因的表达，表明这一淋巴细胞特异性的转录因子能够促进实体肿瘤的转移，提示SpiB的异位表达很可能是小细胞肺癌具有高转移特性的关键因素之一。本项目将利用裸鼠肺内注射模型、3C、ChIP等技术研究SpiB是否通过上调MMP9和PLGF来促进小细胞肺癌的转移以及调控这些基因表达的表观遗传机制，并利用临床肺癌组织芯片研究SpiB的异位表达与临床肺癌转移的相关性，研究结果将丰富人们对于实体肿瘤转移的分子机制的理解，为实体肿瘤的治疗提供新的思路。

中文关键词： C05_气管；支气管；肺肿瘤；SpiB；肿瘤转移；小细胞肺癌；染色体构象俘获

英文摘要： Compared with NSCLC, SCLC generally has a more rapid doubling time, a higher growth fraction, and earlier development of widespread metastases. To understand the molecular mechanism of cancer distal metastasis, we examined gene expression profiling in SCLC using RNA-Seq and found that SCLC expresses a series of transcription factors normally restricted to lymphoid cells, including SpiB. Overexpression of SpiB significantly increased the lung metastasis of LLC1 and promoted the expression of invasion-related genes, such as MMP9 and PLGF. These data suggest that SpiB might be a signature of SCLC and its ectopic expression increase the malignancy. Here, the objective of this project is to focus on the function and regulation of SpiB in tumor metastasis using multiple techniques including orthotopic nude mouse models, 3C, immunohistochemistry, RNA interference and ChIP. Specifically, we will dissect the connection between SpiB expression level and distal metastasis of lung cancer through tissue microarray, and the role of ectopic expression of SpiB in tumor invasion and tumor cells transendothelial migration. The results will shed a light in understanding the molecular mechanism of tumor cell metastasis and may provide a new target for the tumor treatment.

英文关键词： lung cancer;SpiB;tumor metastasis;SCLC;chromatin conformation capture