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MiR133s Inhibits Proliferation Of Lung Adenocarcinoma Cells By Targeting SOX4 And Regulating Protein Regulator Of Cytokinesis 1

Posted on:2019-08-11Degree:MasterType:Thesis
Country:ChinaCandidate:M Y LiFull Text:PDF
GTID:2404330572953299Subject:Biological products
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At present,most researchers believe that the occurrence of cancer stems from abnormal cell proliferation.Protein regulator of cytokinesisl(PRC1)plays an important role in cytokinesis and is a key protein in cytokinesis.According to the existing research literature,PRC1 is highly expressed in cancer cells such as breast cancer,lung adenocarcinoma,liver cancer,and gastric cancer,and promotes invasion and metastasis of lung adenocarcinoma cells through Wnt/β-catenin signaling pathway,but PRC1 is involved in lung adenocarcinoma.The specific mechanism of abnormally high expression in cells remains unclear.SOX4(SRY related high mobility group box 4)is a member of the SOX family.As an important transcription factor,it can bind to the oncoprotein c-myc to promote the occurrence and development of lung cancer.Through bioinformatics analysis,we found that there is a binding site for SOX4 in the promoter region of PRC1 gene.In addition,as a regulator of the Epithelial-Mesenchymal Transition(EMT),SOX4 has also been shown to be a target of has-miR-133a-3p,thereby inhibiting the migration and invasion of esophageal cancer cells,but Whether there is a similar role in lung adenocarcinoma has not been reported in the literature.In the first part of the experiment,we first determined the high expression of PRC1 in lung adenocarcinoma by real-time fluorescent quantitative PCR and Western blotting.Next,bioinformatics analysis predicted that SOX4 may act as a transcription factor to regulate the expression of PRC1 and in H1299 cells.By knocking down the vector to inhibit the expression of SOX4,it was verified that the expression level of PRC1 decreased with the decrease of SOX4 expression.The double luciferase reporter experiment further proved that SOX4 can bind to the promoter region of PRC1.In the second part,we predicted that miR-30s and miR-133s can target SOX4-3’UTR through online tools.The expression of miR-133s in lung adenocarcinoma was confirmed by real-time fluorescent quantitative PCR detection of the expression levels of these two miRNA families.Abnormally low expression.Using miRNA mimics to overexpress miR-133s in H1299 cells,the expression levels of SOX4 and PRC1 were significantly reduced.The dual luciferase reporter assay further demonstrated that miR-133s(hsa-miR133a-3p and hsa-miR133b)can be targeted.The SOX4-3’UTR inhibits the expression of SOX4,thereby inhibiting the proliferation of lung adenocarcinoma cells and promoting apoptosis.
Keywords/Search Tags:Lung adenocarcinoma, Protein regulator of cytokinesis 1, SOX4, miR-133s
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