研究背景:乳腺癌(Breast cancer,BC)是全世界女性最常見(jiàn)的惡性腫瘤,其死亡率位居女性惡性腫瘤的首位。目前已明確侵襲和轉(zhuǎn)移是乳腺癌的主要生物學(xué)特征,是一個(gè)多步驟、多因素共同參與的連續(xù)過(guò)程,也是導(dǎo)致乳腺癌患者死亡的主要原因。隨著乳腺癌分子生物學(xué)研究的進(jìn)展,針對(duì)不同分期、細(xì)胞受體、分子分型等的靶向治療成為臨床研究熱點(diǎn),推動(dòng)了乳腺癌治療實(shí)現(xiàn)“個(gè)體化”的進(jìn)程。自1998年首次批準(zhǔn)分子靶向藥物曲妥珠單抗應(yīng)用于實(shí)體腫瘤治療以來(lái),涌現(xiàn)了越來(lái)越多的分子靶向治療藥物,如CDK4/6抑制劑呢泊塞克雷(Palbociclib)、雌激素拮抗劑他莫昔芬(Tamoxifen)、mTOR靶蛋白的抑制劑依維莫司(Everolimus)等。這些藥物的臨床應(yīng)用雖然顯著提高了乳腺癌的治療效果,但針對(duì)轉(zhuǎn)移性乳腺癌患者的預(yù)后依舊欠佳。因此,深入研究乳腺癌侵襲和轉(zhuǎn)移的分子機(jī)制并尋找有效的治療靶點(diǎn),對(duì)于研發(fā)新型分子靶向藥物、改善轉(zhuǎn)移性乳腺癌患者的預(yù)后和生存質(zhì)量具有重要意義。微小RNA(miRNAs)是一種內(nèi)源性的非編碼小分子RNA,長(zhǎng)度約為18-25個(gè)核苷酸。miRNA可通過(guò)與特定mRNA的3'-UTR(3'-非翻譯區(qū))...

【文章頁(yè)數(shù)】：104 頁(yè)

【學(xué)位級(jí)別】：博士

【文章目錄】：
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
攻讀博士學(xué)位期間取得的科研業(yè)績(jī)
致謝



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