miRNA通过3’UTR对PD-1和CTLA-4基因的调控在HBV感染中的作用

Programmed cell death–1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) are all important immunosuppressive molecules in regulating T cell immune function and associated with HBV infection. miRNAs, a class of small non-coding RNA molecules, play a key role in regulating the expression of mRNA and its protein via specific binding to the target 3' untranslated region (3'UTR) of mRNA. The differences of SNP, located in the 3'UTR of PD1 and CTLA-4 gene, may affect PD-1 and CTLA-4 mRNA expression, leading to the alteration of immune regulation and disease process in HBV infection. Based on previous studies, the aim of the study is to aim to investigate some miRNAs, which putatively bind to the 3’UTR of PD-1 and CTLA-4 mRNA using bioinformatics. Then the miRNAs are designed and synthesised to investigate how the miRNAs regulates PD-1 and CTLA-4 and influences on PD-1 and CTLA-4 expression in vitro. Animal experiments will be used to verify the miRNAs, which may affect HBV infection by regulating the expression of PD-1 and CTLA-4 through interaction with the 3'UTR of them. These studies will shed light on understanding the relationship between different state regulation of PD-1 and CTLA-4 with HBV susceptibility and disease progression, to provide the basis for disease prevention based on genetic information.

PD-1和CTLA-4负性调节T细胞的激活和外周免疫耐受，与HBV感染密切相关。miRNA与基因3'UTR的靶位点结合后，可负性调控靶mRNA的转录，影响靶基因的表达。位于PD-1和CTLA-4基因3'UTR的SNP差异可导致PD-1和CTLA-4 mRNA表达及其对免疫调控的改变，从而影响疾病过程。本课题在前期研究基础上，拟进一步用生物信息学技术，寻找PD-1和CTLA-4基因3'UTR对应的miRNA，设计合成miRNA并在体外探讨miRNA对PD-1和CTLA-4 3'UTR的调控作用及其对PD-1和CTLA-4表达的影响。通过动物实验，明确miRNA 通过3'UTR对PD-1和CTLA-4基因的调控在HBV感染中的作用。为在基因水平理解PD-1和CTLA-4的不同调控状态与HBV易感性和疾病进展的关系，为基于基因信息的疾病防治提供依据。