OVOL2 Inhibits EMT By Downregulating NF-KB Signaling And MMP9

As a transcription factor,Ovol2 plays an important role in the genesis and development of breast cancer,colorectal cancer and other tumors.However,the research of the role of ovol2 in liver cancer as the top 10 incidence of all cancer in the world is relatively not so much.In our experiments,we found that the expression of Ovol2 in liver cancer cells was less than that in normal cells.And Ovol2 can inhibit the expression of matrix metalloproteinase 9(MMP9)in hepatoma cells.MMP9 plays an important role in the invasion and metastasis of cancer by degrading collagen type IV and extracellular matrix,,and can be used as a marker of EMT.Through cell scratching and transwell experiments and the detection of EMT-related factors,we confirmed that ovol2 inhibits the EMT process in liver cancer cells.Considering that NF-KB can bind directly to the promoter of MMP9 and regulate EMT,we speculate that if ovol2 would affect the EMT process through the NF-KB signaling pathway.So we carried out further research.Through luc experiments,we confirmed that ovol2 has a significant inhibitory effect on TNF-a-activated NF-kB signaling,and it also significantly down-regulates the downstream target genes of NF-KB.We then wanted to explore the mechanism by which Ovol2 affects NF-KB.Numerous articles in the study of NF-KB have shown that P65 is the core protein in the classical pathway.By co-immunoprecipitation experiments we confirmed that ovol2 can interact with P65.The above experiments show that ovol2 may inhibit EMT by interacting with P65,inhibiting the activity of NF-KB pathway,and the expression of downstream target genes.This provides new insights into the role of ovol2 in cancer research.