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SOX13 Complex Promotes Invasion And Metastasis In Hepatocellular Carcinoma Via Raising TWIST1

Posted on:2019-08-12Degree:MasterType:Thesis
Country:ChinaCandidate:M FengFull Text:PDF
GTID:2404330545983553Subject:Surgery
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BackgroundPrimary hepatocellular carcinoma(also called HCC)is one of the world’s common malignant tumor,its incidence and mortality is rising worldwide.Primary liver cancer major epidemic area of southeast Asia area,secondly in Africa,and a handful of Europe,the americas and other regions,the cause of the high incidence and the prevalence of hepatitis b virus and residents’ income.In our country,primary liver cancer incidence,mortality,ranked the first three of malignant tumor.Treatment of liver cancer with tumor lesions,radiation and chemotherapy as well as the secondary biological treatment.The present situation,liver metastasis progress fast,surgical treatment and other invasive treatment method will not be able to effectively delay the survival prognosis of advanced liver cancer patients.So the current research direction is that biological treatment and molecular targeted therapy,its main purpose is to diagnose and prevent the late in cirrhosis or early tumor,or after the tumorigenesis of inhibiting tumor metastasis.By means of one or more specific indicators of control to prevent intracellular signaling pathways of disorder and the control ability of the cell proliferation and tumor.Tumor cell invasion ability get very complicated,often with the help of a variety of protein factor,then can be directly involved in the transcription of DNA seemed particularly important.The Sox gene family are known to be involved in the formation of the embryonic development and mature,determined cell fate and differentiation.In recent years,more and more literatures show that SOXs protein up-regulated in a wide variety of tumor and become an independent risk factor for cancer,some of the important members of the family such as SOX2,SOX4 involved in breast cancer,lung cancer,liver cancer and other tumors,participated in tumor epithelial-mesenchymal transition and stem cells self-renew,etc.Hence,we decided to study SOXs protein transcription of liver cancer cells and its regulatory mechanism.In this study,we according to verify the amount of the SOX family protein expression in liver cancer found SOX13 significant increase in cancer of the liver tissue,preliminary think SOX13 is related to the transfer of liver cancer and differentiation,and further study of its regulating mechanism and clinical significance.AimsIn liver cancer specimens,figure out SOX13 expression in tumor tissue and para-tumor tissue,and clinical pathology of statistical analysis,to determine the correlation between the expression of SOX13 and clinical indicators of liver cancer.To further explore SOX13 regulatory mechanism of the malignant phenotype in liver cancer,and to fulfill liver cancer molecular regulation network,SOX13 as forecast and provide theoretical basis for therapeutic targets.Methods1,pathological specimens in check and analyze SOX13 SOX13 expression and clinical indicators,survival prognosis and risk factors.Gain and loss of cells 2,build SOX13 function,detecting SOX13 in the in vivo and in vitro experiments on tumor cell migration,invasion and the influence of colonize ability.3,by detecting the downstream gene expression quantity determine SOX13 signaling pathways of influence.4,confirmed by molecular biology experiments SOX13 formed by complex plays an important role in the regulation of the downstream genes Twist1.Results1,SOX13 significantly higher expression in liver cancer tissue,and is associated with tumor metastasis,differentiation of clinical indicators,SOX13 expression can lead to overall survival of liver cancer,liver cancer to reduce postoperative disease-free survival,SOX13 high expression is also an independent risk factors for liver cancer patients.2,experiments show interference SOX13 expression in vivo and in vitro can inhibit the liver cancer cell invasion and metastasis ability.3,SOX13 through raising Twistl expression which affect liver cancer cells of EMT promote liver cancer cell invasion and metastasis.4,SOX13 through combined with SOX5 complex formation,promote the expression of Twist1.Recruitment of different functional protein of Twistl epigenetic regulation.Conclusion1,SOX13 significantly higher expression in liver cancer tissue,associated with the malignant phenotype and survival after liver cancer cells.2,SOX13 promote Twistl transcription by and SOX5 form complex,thus promotes the transfer of liver cancer.3,SOX 13 compounds by recruiting different exercise the epigenetic regulation of proteins,and other functions.
Keywords/Search Tags:primary liver cancer, SOX13, TWIST1, EMT, epigenetic modifications
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