Demethylase FBXL10 Proliferate Mammarycarcinoma By Repressing FOXC1 Gene Expression

FBXL10 gene is a member of the largest histone demethylase Jmjc subfamily,and it is mapped to chromosome 12q24.31,has H3K4me3 and H3K36me2/1-specific demethylase activity.FBXL10 also known as JHDM1B(Jmjc domian-containing histone demethylase 1B),KDM2B(lysine (K)-specific demethylase 2B),Ndy-1(Not dead yet-1)。FBXL10 protein has a conserved Jmjc demethylase active domain,CXXC DNA-bingding domain,PHD domain,proline-rich domain,F-box domain and leuine-rich repeat domain.According to the different context of the cells,there is controversy about the function of the FBXL10 on the cancer progression,and it is known that FBXL10 overexpressed in human lymphomas and mammary adenocarcinomas.Transcription factor FOXC1 is a member of the Forkhead box(FOX) family,possess a transactivation domain,a DNA-bingding domain and some other domains.We discovererd that the expression of FBXL10 gene was negatively correlated to the FOXC1 between two different breast cancer cell lines MCF-7 and MDA-MB-231,and FBXL10 could transcriptionaly regulate the expression of FOXC1 gene by overexpress and RNAi experiment.The research in my lab discovered that overexpression of FOXC1 inhibited proliferation,and EZH2 could represss FOXC1 gene by impacting its histone H3K27 tri-methylation and acetylation modifications.However,it is unreported that the function of histone demethylase FBXL10 in the breast cancer and if the process is related to FOXC1.The aim of our study was to clarify the function of the histone demethylase FBXL10 on the proliferation and if the function is related to FOXC1.Through MTT,we found that overexpression of FBXL10 could promote proliferation of MCF-7 and by DLR,Reverse Transcription PCR and western blot assays,we found that FBXL10 inhibited FOXC1 expression.The data presented in this thesis demonstrated the function of FBXL10 to the proliferation of breast cancer cells,and FOXC1 is a new target of FBXL10 protein.The study lays the foundation for the research of the function FBXL10 protein and its transcription regulation mechanism,meanwhile it provides the clues for the biological function of FBXL10.