miR-122是肝细胞中表达最丰富的一类小分子RNA，参与肝炎病毒感染及肝癌细胞凋亡。Toll样受体4（TLR4）能识别肝炎病毒，参与免疫防御及肿瘤的免疫逃逸。我们前期研究发现miR-122可与TLR4靶向结合，且可以抑制TLR4 mRNA的表达，推测其可能参与TLR4介导的天然免疫过程，从而影响肿瘤发生发展。为此，本课题拟进行三方面研究：① miR-122与TLR4表达的相关性研究；② miR-122在TLR4 mRNA上的靶点确认；③ miR-122的沉默与过表达对TLR4下游天然免疫因子表达及肝癌细胞特性的影响。综合分析，明确miR-122通过调节TLR4的表达，从而影响TLR4下游的天然免疫因子的表达及功能，可能参与肝癌的发生发展过程，揭示miR-122调节天然免疫的新分子机制，具有创新性。本研究不仅为研究miRNA与天然免疫的相关性提供依据，更为研究其在肿瘤发生中的作用提供基础。

miR-122 is most abundant in liver and extensively involved in hepatitis virus infection and apoptosis of hepatoma cells. Toll-like receptor 4(TLR4) is expressed in a varity of tumors, and TLR4 activation can promote the apoptosis resistance and invasion of tumors. Using RNAhybrid software we found the predicted binding of complementary sequences between miR-122 and TLR4 mRNAs. Over-expression of miR-122 experiment demonstrated that miR-122 could specifically inhibit TLR4 transcription, may be important for the involvment of miR-122 on the host innate immunity mediated by TLR4. Therefore, the subject intends to identify the correlation from three aspects: (1) correlation studies between miR-122 and TLR4 expression, (2) confirmation of the targets of miR-122 in TLR4 mRNA, (3) influence of miR-122 over-expression/down-expression on the expression of natural immune factors of TLR4 downstream and the hepatoma cells characteristics. Based on the results, we aim to confirm that miR-122 might regulate host innate immunity by adjusting the TLR4 expression to participate in the occurrence of hepatoma development process, which reveals a new molecular mechanism of miR-122 on the regulation of innate immunity. This study provides basis not only for research of miRNA and natural immune but also for the study of miRNA and neoplasm occurs.