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Research On TET1 In Metastasis Of Colorectal Cancer Cell Line DLD1

Posted on:2018-11-19Degree:MasterType:Thesis
Country:ChinaCandidate:Y LiuFull Text:PDF
GTID:2334330563452544Subject:Biology
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Colorectal cancer(CRC)is the third largest global cancer diagnosis,is an important cause of cancer-related deaths.Studies have pointed out that metastatic invasion is the basic characteristics of malignant tumors and important signs,but also the leading cause of death.Among them,epithelial mesenchymal transition(EMT)is one of the important mechanisms to promote migration and invasion.According to the latest study,epigenetic modification plays an increasingly important role in the process of tumorigenesis.TET1 gene plays an important role in the process of hydroxymethylation as a key gene in TET family.In recent years,histone methylation has become more and more important in the change of CRC.This epigenetic modification promotes CRC development by influencing cancer-related factors.So the current situation for TET1 gene in colon cancer malignant metastasis is very urgent.TET1,as a key gene for epigenetic regulation,had played a key regulatory role in the EMT pathway.We found that knocked down the level of TET1 in DLD1 cells can inhibited epithelial markers such as E-cadherin expression and regulate upregulation of the mesenchymal marker N-cadherin at the protein and mRNA level,Twist,Snail1 and Snail2 were used to induce EMT pathway in colorectal cancer cells.In addition,we found that knocked down of TET1 in DLD1 cells could promoted the proliferation,migration and invasion in colorectal cancer cells.This phenomenon indicated that TET1 as a tumor suppressor gene,low expression of TET1 gene could promoted colorectal cancer cell DLD1 malignant metastasis.In the course of histone methylation,EZH2 and UTX1 are two important histone-modifying enzymes.We found that knocked down TET1 gene level in DLD1 could promote the expression of EZH2 and inhibited the expression of UTX1.In addition,the effect of overexpression of UTX1 on the proliferation,migration and invasion of colorectal cancer cells was observed.The overexpression of EZH2 could promoted the proliferation and migration of colorectal cancer cells.In summary,TET1 with histone methylation regulation plays an important role in CRC metastasis.To explore the mechanism of hydroxylation and related genes in tumor metastasis can provide a new idea for the later development of drugs targeted to regulate tumor metastasis.
Keywords/Search Tags:Tumor metastasis, epithelial mesenchymal transition, TET1, histone methylation
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