NQO1/PKLR通过糖代谢重编程调控乳腺癌演进的机制研究
发布时间：2021-04-17 21:11
研究背景:乳腺癌是全球常见的恶性肿瘤之一,也是导致女性死亡的重要原因之一。作为一种异质性疾病,其以不同的激素受体表达状态为特征,而这些特征也常用于预测乳腺癌不同亚型的靶向治疗。目前,临床上已有多种治疗乳腺癌的靶向药物,如雌激素受体（ER）靶向药物--他莫昔芬、HER2靶向药物--曲妥珠单抗。以上靶向药物虽然可有效抑制乳腺癌的演进,但侵袭和转移仍是导致乳腺癌患者死亡的主要病因。因此,深入探究乳腺癌侵袭转移的相关调控基因及分子通路作用机制,将有利于明确乳腺癌的早期诊断及治疗靶点,对改善乳腺癌的个体化治疗及改善患者的预后具有重要临床价值。醌氧化还原酶（NAD（P）H:quinone oxidoreductase-1,NQO1）,也被称为DT-硫辛酰胺脱氢酶,定位于染色体16p22。它通过受体NAD（P）H催化醌类及其衍生物,使其失去双电子发生还原反应,避免了对细胞的损伤。值得注意的是,当NQO1cDNA609位点发生突变时可导致细胞解毒致癌物的能力降低,增加致癌物的作用,导致某种易感个体发生恶性病变,从而增加个体罹患多种恶性肿瘤的危险。近年来,NQO1在多种恶性肿瘤中所扮演的角色备受学者的关...
【文章来源】：延边大学吉林省 211工程院校
【文章页数】：106 页
【学位级别】：博士
【文章目录】：
中文摘要
ABSTRACT
ABBREVIATIONS
1. INTRODUCTION
2. MATERIALS AND METHODS
2.1 Materials
2.1.1 Experimental reagents and instruments
2.2 Methods
2.2.1 Cell culture
2.2.2 Cell viability assay
2.2.3 Transtection
2.2.4 Stable cell line generation
2.2.5 TCGA BC cohorts
2.2.6 Wound healing assay
2.2.7 Colony-forming assay
2.2.8 EdU assay
2.2.9 Immunofluorescence
2.2.10 Migration assay
2.2.11 Invasion assay
2.2.12 Western blot
2.2.13 Immunohistochemistry
2.2.14 Measurement of glucose, lactate, and ATP
2.2.15 Co-Immunoprecipitation （Co-IP）
2.2.16 In vivo tumorigenesis and metastasis assays
2.2.17 Statistical analysis
3. RESULTS
3.1 NQO1 overexpression correlates with poor prognosis in BC
3.2 NQO1 enhances tumor growth and in vivo tumorigenesis
3.3 NQO1 induces epithelia-mesenchymal transition and promotes cellular migration and invasion
3.4 NQO1 promoted BC cell growth and metastasis via regulating glycolysis reprogramming
3.5 Identification of PKLR as a target gene of NQO1 in BC
3.6 The NQO1/PKLR axis regulated the AMPK and AKT/mTOR pathways to modify BC EMT and glycolysisreprogramming
3.7 PKLR is inversely correlated with the expression of NQO1 in normal and breast cancers
4. DISCUSSION
5. CONCLUSIONS
REFERENCES
攻读博士学位期间取得的科研业绩
致谢
本文编号：3144148
【文章来源】：延边大学吉林省 211工程院校
【文章页数】：106 页
【学位级别】：博士
【文章目录】：
中文摘要
ABSTRACT
ABBREVIATIONS
1. INTRODUCTION
2. MATERIALS AND METHODS
2.1 Materials
2.1.1 Experimental reagents and instruments
2.2 Methods
2.2.1 Cell culture
2.2.2 Cell viability assay
2.2.3 Transtection
2.2.4 Stable cell line generation
2.2.5 TCGA BC cohorts
2.2.6 Wound healing assay
2.2.7 Colony-forming assay
2.2.8 EdU assay
2.2.9 Immunofluorescence
2.2.10 Migration assay
2.2.11 Invasion assay
2.2.12 Western blot
2.2.13 Immunohistochemistry
2.2.14 Measurement of glucose, lactate, and ATP
2.2.15 Co-Immunoprecipitation （Co-IP）
2.2.16 In vivo tumorigenesis and metastasis assays
2.2.17 Statistical analysis
3. RESULTS
3.1 NQO1 overexpression correlates with poor prognosis in BC
3.2 NQO1 enhances tumor growth and in vivo tumorigenesis
3.3 NQO1 induces epithelia-mesenchymal transition and promotes cellular migration and invasion
3.4 NQO1 promoted BC cell growth and metastasis via regulating glycolysis reprogramming
3.5 Identification of PKLR as a target gene of NQO1 in BC
3.6 The NQO1/PKLR axis regulated the AMPK and AKT/mTOR pathways to modify BC EMT and glycolysisreprogramming
3.7 PKLR is inversely correlated with the expression of NQO1 in normal and breast cancers
4. DISCUSSION
5. CONCLUSIONS
REFERENCES
攻读博士学位期间取得的科研业绩
致谢
本文编号：3144148
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