MAF1调控MAPK-ERK信号通路的分子机制及其在肝癌细胞生长中的作用

Liver cancer seriously harms people’s health. Due to the incapacities of understanding the origin and development of it, liver cancer has limited ways of treatment. The of MAPK-ERK signal pathways correlate with the growth of hepatocarcinoma cells. Such connection is the focal point of its treatment. MAF1 is a regulatory protein for the gene transcription. Previous studies have shown that MAF1 can inhibit the growth of hepatocarcinoma cells, but its mechanism of inhibiting the growth of hepatocarcinoma cells, especially the mechanism of transcriptional regulation, remains unknown. Moreover, MAF1 can regulate the acetylation of histones. However, the molecular mechanism of MAF1-modulating, the MAPK-ERK signaling pathway, and whether its regulation of the MAPK-ERK signaling pathway is mediated by its transcriptional regulatory function, have not been reported. .Therefore, this study aims to elucidate the molecular mechanism of MAF1-regulated MAPK-ERK signaling pathway by immunoprecipitation, chromatin immunoprecipitation-sequencing, in vitro / in vivo experiments and analysis of clinical liver cancer specimens. The goal of this study is providing a new perspective for the targeted therapy and the innovation of new medicines.

肝癌严重危害人类健康，但治疗手段有限,主要是因为其发生、发展机制仍不清楚。MAPK-ERK信号通路的过度活化与肝癌细胞的生长密切相关,是肝癌治疗的重要靶点。MAF1是一个基因转录的调节蛋白。以往的研究证明MAF1可以抑制肝癌细胞生长，但其抑制肝癌细胞生长的机制，特别是转录调节的机制尚不清楚。我们的前期研究发现MAF1可以通过调节MAPK-ERK信号通路抑制肝癌细胞的生长，并且还可以参与调节组蛋白的乙酰化。然而，MAF1调节MAPK-ERK信号通路的分子机制，以及其对MAPK-ERK信号通路的调控是否由其转录调节功能所介导，尚未见相关报道。因此，本项目拟采用免疫共沉淀、染色质免疫共沉淀-测序技术、体外/体内实验以及结合临床肝癌标本分析等方法，深入研究MAF1调控MAPK-ERK信号通路的分子机制，旨在阐明MAF1在肝癌细胞生长中的作用，为提高靶向治疗效果及研发新的靶向药物提供新的思路。