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The Roles Of MicroRNA-149-3p In Esophageal Cancer Cells

Posted on:2021-02-13Degree:MasterType:Thesis
Country:ChinaCandidate:L ZhangFull Text:PDF
GTID:2404330605471578Subject:Pharmaceutical engineering
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Esophageal cancer(EC)is the sixth most deadly cancer in the world.And the incidence rates for EC have increased year by year.China has nearly half of the world's total of esophageal cancer and China is one of high incidence district of esophageal cancer in the world.Recent scientific research has made the latest development in the esophageal cancer diagnosis and treatment,but its prognostic and survival rate are still low,and its pathogenesis is still not well known.In order to reduce the mortality of esophageal cancer and find new treatment,it has important significance to research on the molecular mechanism of esophageal cancer and explore its new effective therapeutic targets.microRNAs(miRNAs)are small non-coding RNAs that can act on the 3'UTR or 5' UTR sequences of target genes through base-pairing to regulate translation and participate in multiple physiological and pathological process-es.Research shows that the abnormal expression of miRNAs is perhaps the way to inhibit cancer or as the tumor promoter.These scientific conclusions indicate miRNAs may be new therapeutic targets for treating cancer.AKT signaling pathway plays a significant role in cell survival,prolifera-tion and apoptosis.It can regulate multiple interrelated signal transduction pathways such as cell metabolism,growth,division,apoptosis and other pro-cesses.The NF-?B signaling pathway is closely related to the physiological processes of inflammation and cancer.It can regulate many cell physiological processes such as cell proliferation,apoptosis and angiogenesis.JNK is an-other subclass of MAPK signaling pathway,and the signaling pathway can regulate various physiological and pathological processes of various diseases.Therefore,AKT,NF-?B and JNK signaling pathways has important research value as a target for treating cancer.In this work,we conducted a fuctional research using the human esopha-geal cancer cell line KYSE150.In cellular phenotype level,RTCA showed that miRNA-149-3p can inhibit proliferation of esophageal cancer cells.Through Annexin-V-FITC/PI double-staining method,we found that miR-NA-149-3p could promote apoptosis of esophageal cancer cells.In the reseach of molecular mechanism level,using real-time PCR assay,miRNA-149-3p can inhibit the gene expression of IL-6,CCL-2 and COX-2.Meanwhile,miR-NA-149-3p can inhibit the expression levels of these inflammatory genes after induced with TNF-?.Western blot results showed that miRNA-149-3p can in-hibit the phosphorylation of AKT in esophageal cancer cells.Furthermore,we found that miRNA-149-3p can inhibit the expression levels of PDK1,TRAF6,TLR4,BCR and CDC37 upstream of the AKT pathway.In addition,through Western blot test,we also found that miRNA-149-3p can inhibit the phosphorylation of JNK and the phosphorylation of I?B? in esophageal cancer cells.In summary,miRNA-149-3p has negative regulatory effect on esophage-al cancer cells.This conclusion may provide a new target and strategy for the prevention and treatment of esophageal cancer in the future.
Keywords/Search Tags:microRNA-149-3p, Esophageal Cancer, AKT signaling pathway, NF-?B signaling pathway, JNK signaling pathway
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