LAIR-1在卵巢癌的表达及其对卵巢癌细胞增殖和侵袭能力的影响

LAIR-1是以胶原为配体的免疫抑制性受体。我们近期首次利用免疫组化的方法在卵巢癌组织芯片中发现LAIR-1在卵巢癌细胞表达，肿瘤分级越高LAIR-1的表达越高，提示LAIR-1是促癌蛋白；我们在多种卵巢癌细胞株也发现LAIR-1的表达；但是，shRNA干扰LAIR-1基因在卵巢癌细胞株HO8910的表达，发现LAIR-1抑制HO8910的增殖和侵袭。因此，LAIR-1在卵巢癌的作用需要深入研究。本项目拟在前期工作基础上，利用qRT-PCR、Western blot、RNA干扰、CRISPR/Cas9编辑等技术以及卵巢癌裸鼠原位移植瘤模型，明确LAIR-1在卵巢癌组织的表达、临床意义及在卵巢癌增殖和侵袭中的作用；采用基因芯片、抗体芯片分析LAIR-1在卵巢癌增殖和侵袭相关的重要信号通路中的作用。本项目的研究将进一步阐明卵巢癌致病机制、为早期诊断试剂和靶向治疗药物的开发提供新的依据。

LAIR-1 is a collagen receptor which belongs to the immune inhibitory receptor family. In our recent study, we showed for the first time that LAIR-1 was expressed in ovarian carcinoma cells in a tissue microarray using immunohistochemical staining, and the expression of LAIR-1 was positively associated with higher grade tumor, which suggests that LAIR-1 maybe a carcinogenic factor. Besides, the expression of LAIR-1 was also detected in several ovarian carcinoma cell lines, but down-regulation of LAIR-1 expression by lentivirus-mediated shRNA in HO8910 cells showed that LAIR-1 reduced cell proliferation, colony formation and cell invasion of HO8910 cells. The role of LAIR-1 in the pathogenesis of ovarian cancer need to be further investigated. The project is intended to use shRNA gene knockdown strategy, CRISPR/Cas9 system, as well as nude-mouse transplanted tumor model to identify the function of LAIR-1 in the cell proliferation and invasion of ovarian carcinoma. We will use qRT-PCR, Western blot to identify in mRNA and protein level the expression of LAIR-1 and its clinical significance in ovarian carcinoma. Then, we will further investigate the effect of LAIR-1 on the signal pathways related to cell proliferation and invasion by using gene microarray, antibody microarray. . This study may be helpful for a better understanding of molecular pathogenesis of ovarian cancer, and may provide new idea for the development of early diagnostic reagents and targeted- therapy drugs.