miR-20b介导ERK信号通路在PCBs暴露致子代视网膜发育异常中的作用机制研究

miR-20b, a kind of miRNA which is screened from miRNA array, is significantly increased in zebrafish retinal after embryonic exposed to PCBs and is highly conserved between species. It is found that miR-20b mimics can cause abnormal retinal development by inhibiting proliferation and promoting apoptosis of retinal photoreceptor cells. Bioinformatics analysis and experiment show that FGF2 and GRB2 are candidate targets of miR-20b. FGF2 and GRB2 are upstream of MAPK/ERK signaling pathway, and the phosphorylation levels of the downstream RAS and ERK both decreased after PCBs exposure. To demonstrate the hypothesis, our study use overexpression, silent strategy and save test to verify that the mechanism of miR-20b mediating ERK signaling pathway on the retinal development after exposed to PCBs. This study is innovative, and help to clarify the mechanism of PCBs exposure on retinal development, providing new Intervention targets for the prevention and treatment of retinal diseases caused by environmental pollutants.

miR-20b是我们通过miRNA芯片筛选的、在胚胎期PCBs暴露的斑马鱼视网膜组织中高表达且高度保守的一条miRNA。前期实验证实miR-20b过表达可抑制视网膜感光细胞增殖，促进其凋亡，进而导致视网膜发育异常。生物信息学分析及预实验证实FGF2、GRB2可能是miR-20b下游的靶标。FGF2及GRB2位于MAPK/ERK信号通路上游，且PCBs暴露RAS及ERK磷酸化水平降低。本研究拟采用过表达/沉默技术及挽救实验，以FGF2和GRB2为机制线索，系统阐明miR-20b介导MAPK/ERK信号通路在PCBs暴露致子代视网膜发育异常中的作用机制。由于miR-20b在胚胎期PCBs暴露致视网膜发育异常国内外未见报道，本研究具有源头创新性，有望为环境污染物暴露致视网膜疾病的防治提供新的干预靶标。

视网膜发育异常是儿童弱视等眼病发生的重要原因，但其具体机制尚不明确，本课题主要研究从miRNA角度探讨胚胎期PCBs暴露使后子代视网膜感光细胞发育异常的机制显得十分必要。.miR-20b是我们通过miRNA芯片筛选的、在胚胎期PCBs暴露的斑马鱼视网膜组织中高表达且高度保守的一条miRNA。体外实验证实miR-20b过表达可抑制视网膜感光细胞增殖，促进其凋亡，进而导致视网膜发育异常。生物信息学分析显示FGF2、GRB2是miR-20b下游的靶标。体外细胞实验发现miR-20b抑制FGF2及GRB2表达并导致RAS及ERK磷酸化水平降低，进而影响视网膜感光细胞的增殖和凋亡。体内miR-20b斑马鱼模型进一步验证miR-20b通过调控靶基因FGF2及GRB2表达导致视网膜发育异常。.本研究首次阐明miR-20b介导MAPK/ERK信号通路在PCBs暴露致子代视网膜发育异常中的作用机制。由于miR-20b在胚胎期PCBs暴露致视网膜发育异常国内外未见报道，本研究具有源头创新性，有望为环境污染物暴露致视网膜疾病的防治提供新的干预靶标。