miR-21-5p/Tiam1调控乳腺癌演进的机制研究

发布时间：2025-04-18 00:35

　　研究背景:乳腺癌(Breast cancer,BC)是全世界女性最常见的恶性肿瘤,其死亡率位居女性恶性肿瘤的首位。目前已明确侵袭和转移是乳腺癌的主要生物学特征,是一个多步骤、多因素共同参与的连续过程,也是导致乳腺癌患者死亡的主要原因。随着乳腺癌分子生物学研究的进展,针对不同分期、细胞受体、分子分型等的靶向治疗成为临床研究热点,推动了乳腺癌治疗实现“个体化”的进程。自1998年首次批准分子靶向药物曲妥珠单抗应用于实体肿瘤治疗以来,涌现了越来越多的分子靶向治疗药物,如CDK4/6抑制剂呢泊塞克雷(Palbociclib)、雌激素拮抗剂他莫昔芬(Tamoxifen)、mTOR靶蛋白的抑制剂依维莫司(Everolimus)等。这些药物的临床应用虽然显著提高了乳腺癌的治疗效果,但针对转移性乳腺癌患者的预后依旧欠佳。因此,深入研究乳腺癌侵袭和转移的分子机制并寻找有效的治疗靶点,对于研发新型分子靶向药物、改善转移性乳腺癌患者的预后和生存质量具有重要意义。微小RNA(miRNAs)是一种内源性的非编码小分子RNA,长度约为18-25个核苷酸。miRNA可通过与特定mRNA的3'-UTR(3'-非翻译区)...

【文章页数】：104 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 Clinical specimens and Ethic Statement
        2.1.2 Experimental reagents and instruments
    2.2 Methods
        2.2.1 Cell culture
        2.2.2 Transfection
        2.2.3 Stable cell line generation
        2.2.4 Cell viability assay
        2.2.5 Colony-forming assay
        2.2.6 EdU assay
        2.2.7 Wound healing assay
        2.2.8 Migration assay
        2.2.9 Invasion assay
        2.2.10 Immunofluorescence
        2.2.11 Matrigel tube formation assay
        2.2.12 Glucose uptake, lactate and ATP assays
        2.2.13 Data set
        2.2.14 qRT-PCR
        2.2.15 Luciferase reporter assay
        2.2.16 Western blot (WB)
        2.2.17 Immunohistochemistry (IHC)
        2.2.18 In vivo tumorigenesis and metastasis assays
        2.2.19 Statistical analysis
3. RESULTS
    3.1 Tiaml was up-regulated in BC and predicted poor prognosis
    3.2 Tiaml promoted cell proliferation and tumorigenesis of BC
    3.3 Tiaml promoted BC metastasis via EMT in vitro and in vivo
    3.4 Tiaml promoted angiogenesis in BC
    3.5 Tiaml promoted BC cell growth and metastasis through Warburg effect
    3.6 Tiaml was a direct target of miR-21-5p
    3.7 The miR-21-5p/Tiaml regulated Warburg effect and tumor metastasis in BC
4. DISCUSSION
5. CONCLUSIONS
6. INNOVATION POINTS
REFERENCES
攻读博士学位期间取得的科研业绩
致谢



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