Research On The Roles Of YTHDF1 And YTHDF2 In Hepatocellular Carcinoma Proliferation And Metastasis

As a kind of malignant tumor with high mortality and morbidity,liver cancer seriously threatens the health of humans.Today,the methods of diagnosis and treatment for liver cancer patients are poor,and the 5-year survival rate of liver cancer patients is very bad.Therefore,it is very important to reveal the pathogenesis of liver cancer.In recent years,with the continuous research on RNA modifications,the importance of m6 A in cancer has become increasingly prominent.And m6 A provides some new ideas for the molecular mechanism of cancer development.However,the role of m6 A in hepatocellular carcinoma(HCC)has not been fully elucidated.For the above reasons,four datasets containing high-throughput sequencing or gene chip data of HCC samples from TCGA and GEO databases were analyzed in this paper.The key m6 A regulators METTL3,METTL14,WTAP,FTO,ALKBH5,YTHDF1 and YTHDF2 were selected to analyze their expression pattern in HCC.The results showed that the expression of YTHDF1 and YTHDF2 in HCC tissues were significantly higher than that in para-cancer tissues.Survival analysis showed that patients with high YTHDF1 and YTHDF2 expression had worse overall survival(p < 0.001 and p < 0.001,respectively)and disease-free survival(p= 0.0116 and p=0.002,respectively).In addition,combined with the clinical data of HCC patients,it was found that the high expression of YTHDF1 and YTHDF2 was associated with the progression of HCC.Gene set enrichment analysis suggested that YTHDF1 was associated with DNA replication and extracellular matrix interaction in HCC cells.And YTHDF2 was related to HCC cell cycle and extracellular matrix interaction.Ch IP-seq data showed that histone H3K4me3 may regulate the expression of YTHDF1 in HCC tissues.Furthermore,YTHDF1 doesn't regulate the proliferation of HCC cells,while the low expression of YTHDF2 significantly inhibited the proliferation of HCC cells.In addition,knock down of YTHDF1 can improve HCC cells' metastasis ability,while YTHDF2 knocked down inhibited the metastasis of HCC cells significantly.