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Regulation Of Menin On P53 In Lung Cancer And Its Biological Significance

Posted on:2018-11-07Degree:MasterType:Thesis
Country:ChinaCandidate:J Q TanFull Text:PDF
GTID:2404330518483119Subject:Microbiology
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Lung cancer and Hepatocellular Carcinoma(HCC)are one of the six most common malignancies in the world and one of the most important causes of death in humans.Multiple endocrine neoplasia type 1(MEN1)is a familial autosomal disease characterized by endocrine organ tumors such as parathyroid,anterior pituitary tumor and islet,and its key pathogenic genes is MEN1,which encodes the menin protein.Our laboratory found that MEN1 as a typical tumor suppressor gene play a role in tumor suppression in lung cancer,and menin inhibits the pulmonary neuroendocrine tumor differentiation.However,MEN1 as a oncogene plays a important role in HCC.Therefore,it is helpful to elucidate that mechanisms of different biological functions of menin in different tumor systems is helpful to reveal the mechanism of cancer-specific pathogenesis,which is of great significance to treat the disease.In this research,hepatocellular carcinoma cell line,non-small cell lung cancer cell line and MEN1-related animal model were used to study the regulation of P53 in two main different cancers.In lung cancer,the expression of Marker in neuroendocrine tumors of MEN1 heterozygous loss mice was confirmed by immunohistochemical reaction,which indicated that menin could inhibit the differentiation of pulmonary neuroendocrine differentiation and the correlation between menin and P53 expression.In lung cancer cells using protein immunoblotting technology to clarify menin can promote the expression of P53,and may be involved in the regulation of H3K4me3.In HCC,menin over-expression inhibited p53 by Western blotting and qRT-PCR in HepG2 cells.It was possible to regulate P53 by mediating H3K4me3,and it was proved that menin inhibited P53 from ubiquitination Enzyme PSMA7 and CUL4 A ubiquitination degradation.This study explored the key biological effects of menin and lung cancer on lung cancer,and clarified the regulation relationship of menin on P53 in these two kinds of cancer systems and explored its regulatory mechanism.The deepening of this study will help to reveal the epigenetic mechanism of the occurrence of cancer,malein and P53 pathway as the target of early diagnosis and treatment of cancer has a positive guiding significance.
Keywords/Search Tags:pulmonary neuroendocrine differentiation, MEN1, p53
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