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The Mechanism Of MiR-10b Regulating Autophagy Is In Esophagy Is In Esophageal Cancer Cells

Posted on:2019-09-01Degree:MasterType:Thesis
Country:ChinaCandidate:Y LuFull Text:PDF
GTID:2404330551957951Subject:Food Science and Engineering
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Because of the special diet,esophageal cancer become a high incidence of Digestive system-related cancer in China.Esophageal cancer(EC)is a high mortality tumor due to the high deaths and late diagnosis.Even the treatment is varied,the side effects are serious.Autophagy is the process of capturing intracellular proteins and organelles and degrading them in lysosomes.Degradation products are released from lysosomes and recycled into metabolic and biosynthetic pathways.Basal autophagy maintains protein and organelle proper function by eliminating damaged cellular components.Starvation-induced autophagy circulates intra cellular components to metabolic pathways to maintain mitochondrial metabolic function and energy homeostasis.What kind of role autophagy plays in the development of cancer,it is always been discussed.miRNAs are small ncRNAs of 19-24 nt in length.miRNAs negatively regulate the expression of a target gene by completely or incompletely binding the 3’-untranslated regions(3’-UTRs)of the target mRNAs,result to targeted mRNA degradation or translational inhibition.It’s possible to treat the cancer using the principle of autophagy in Precision treatment,as long as we link the autophagy and the cancer.This study found that a microRNA can target specific genes in esophageal cancer cells,affecting autophagy and cell proliferation,migration,and invasion.This study suggests that miR-10b can significantly promote autophagy in KYSE450 and KYSE510 cells.Moreover,we found the miR-10b target DAZAP1 through bioinformatics.And confirmed it at the molecular level and protein level,Knocking off the target gene DAZAP1 also promotes autophagy in esophageal cancer cells.At the same time,we also fing DAZAP1 inhibits proliferation,migration,and invasion of esophageal cancer cells through a series of biological function experiments.Because it has been reported that DAZAP1 is often involved in alternative splicing.Through RNA-seq,we have find an increase in the expression of long-chain TSC2 and a decrease in short-chain,then the lack of the S981 site in the short chain inhibits the activation of mTOR by affecting the decrease in the phosphorylation of TSC2,It perfectly explains the mechanism of miR-10b promotes autophagy.Therefore,we can confirm that miR-10b and DAZAPI can be a biological targets for personalized medicine.
Keywords/Search Tags:Autophagy, miR-10b, esophageal cancer, DAZAP1, TSC2, mTOR
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