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Effect Of KLF11 On Stem Cell-like Characteristics Of Sarcoma

Posted on:2020-08-11Degree:MasterType:Thesis
Country:ChinaCandidate:C J ShiFull Text:PDF
GTID:2404330578459419Subject:Surgery
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Background and purpose:Sarcomas can be broadly classified into soft tissue sarcoma or osteosarcoma,a group of mesenchymal malignancies with more than 50 histological subtypes,a heterogeneous collection of rare tumor subtypes with special histological features.The rarity and heterogeneity make the diagnosis particularly difficult,and the diagnosis is mostly in the middle and late stages.The main treatment methods are surgery,radiotherapy and chemotherapy.For local primary tumors,active or standard treatment with or without chemotherapy is usually used,but local recurrence and distant metastasis remain a major problem.Chemotherapy has limited efficacy for most soft tissue sarcomas.Both radiotherapy and conventional chemotherapy reduce local and distant recurrence.However,the effectiveness of radiation therapy is often limited by the location of the disease(eg,retroperitoneal sarcoma),while systemic treatment with conventional chemotherapy regimens has limited efficacy and is often poorly tolerated with significant toxicity.In recent years,more and more scholars believe that the occurrence and development of tumors are closely related to cancer stem cells: the theory of cancer stem cells(CSCs)suggests that only a small number of cells in tumor tissues have self-renewal ability and differentiation potential.It is the root cause of tumorigenesis,development and metastasis.KLF11(kruppel-like factor 11)is a member of the KLFs transcription factor family.Members of the KLFs family are complex and diverse,and participate in cell differentiation,apoptosis and senescence,as well as intercellular adhesion,angiogenesis,glycolipid metabolism and other processes under different tissue or pathologicalconditions.Some of these members(KLF4,etc.)are also involved in somatic cell reprogramming and maintenance of stem cell multi-differentiation potential.It plays a very important role in cardiovascular,respiratory,digestive,endocrine and immune system development and homeostasis.KLF11 is widely expressed in various tissues such as pancreas,muscle,liver and kidney,and participates in regulating various important physiological and pathological processes such as cell proliferation and glycolipid metabolism.The study found that KLF11 expression in lung cancer,pancreatic cancer,ovarian cancer,hematological tumors and other malignant diseases decreased significantly,and its anti-cancer effect was also significantly reduced,this abnormal expression involved in the tumor development process.Although KLF11 has been studied in many cases,the function of KLF11 in human sarcoma has not been reported in detail,especially the role played by tumor stem cell-like properties.The purpose of this study was to investigate the biological role of KLF11 in sarcomas,especially in stem cell properties.In this study,we first found that KLF11 is poorly expressed in sarcoma stem cells with a poor prognosis.Analysis of CSCs loss of function and analysis of sarcoma cell function demonstrated that KLF11 inhibits the self-renewal ability,tumorigenicity and metastasis of sarcoma stem cells.Clinical investigation also confirmed the correlation between KLF11 and prognosis.In conclusion,KLF11 can be used as a new target for sarcoma targeted therapy,providing new ideas for sarcoma treatment.Methods:1.Detection of KLF11 expression in various sarcoma tissues and adjacent tissues in clinical tissue samples The expression of KLF11 in sarcoma tissues and adjacent tissues was analyzed in TCGA and GEO databases.2.Analysis of the effect of KLF11 on the stem cell-like characteristics of sarcoma cell lines: The effects of KLF11 on the stem cell-like characteristics of sarcoma cell lineswere explored using various methods such as pelleting ability test and limiting dilution method.3.To explore the correlation between the expression of KLF11 in the database and the prognosis of patients with sarcoma Result:1.KLF11 is lowly expressed in human sarcoma tissues and cells.2.KLF11 knockdown can promote stem cell-like properties of sarcoma.3.Overexpression of KLF11 can inhibit sarcoma stem cell-like properties.4.Patients with low expression of KLF11 have a poor clinical prognosis.Conclusion: This study shows that KLF11 is underexpressed in sarcoma,and that KLF11 plays an important role in regulating sarcoma stem cell characteristics,and that low expression of KLF11 suggests a poor clinical prognosis.
Keywords/Search Tags:sarcoma, cancer stem cells, KLF11 protein, Prognosis
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