Transcription Factor C-Myc In The Regulation Of Hepatocellular Carcinoma Susceptibility Gene EPB41 Expression And The Biological Function Of EPB41

Hepatocellular carcinoma (HCC)is a kind of extremely malignant liver tumors in China and the prognosis is very poor. As a transcription factor, c-Myc plays a vital role in the development of HCC. After the analysis of c-Myc genome-wide ChIP-chip data in HepG2 cell line, we focused on the single nucleotide polymorphism (SNP) 157224 in the 259 bp of EPB41 gene translation initiation site upstream. It is associated with the risk of HCC in Chinese population, and unfolding the T allele as the risk loci. Using binding site prediction and SNP functional determine experiments in vivo and vitro, reveal that rs 157224 can influence c-Myc binding with its target set. The results suggest that, the G/T polymorphism of rs157224 affects the transcription factor c-Myc binding to EPB41 gene regulation area and it can determine if the expression regulation of c-Myc is turned on or off. The HCC patients more susceptibility taking the TT genotype have less EPB41 protein, and lead to HCC cells malignant proliferation and invasion and metastasis.The studies first found tumor suppressor EPB41 in HCC. A series of molecular and cell biology experiments proved that EPB41 can effectively inhibit the proliferation and suppress migration and invasion and promote the apoptosis in HCC cells.This topic first time revealed the whole genome of the SNP in the transcription factor c-Myc binding sites, and attempts to explain the function of the SNP. It not only found a new suppressor gene, but also further reveals the molecular mechanism of malignant transformation of HCC. It provides a new idea for the early diagnosis and the discovery of HCC therapeutic target.