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研究生: 林佳霓
Lin, Jia-Ni
論文名稱: 轉錄因子SPZ1透過BRAF促進肝癌中的腫瘤生長
Transcription factor SPZ1 promotes BRAF-mediated cell growth in hepatocellular carcinoma
指導教授: 王麗婷
Wang, Li-Ting
口試委員: 賴韻如
Lai, Yun-Ju
許世賢
Hsu, Shih-Hsien
王麗婷
Wang, Li-Ting
口試日期: 2023/07/13
學位類別: 碩士
Master
系所名稱: 生命科學系
Department of Life Science
論文出版年: 2023
畢業學年度: 111
語文別: 中文
論文頁數: 42
中文關鍵詞: 肝癌
英文關鍵詞: SPZ1, BRAF, Hepatocellular carcinoma
研究方法: 實驗設計法
DOI URL: http://doi.org/10.6345/NTNU202301380
論文種類: 學術論文
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  • 致謝 i 摘要 iv Abstract v 目錄 vi 第一章 緒論 1 1-1 肝癌 1 1-2 Spermatogenic leucine zipper 1, SPZ1 2 1-3 BRAF 4 1-4 研究目的 6 第二章 研究材料與方法 7 2-1. 藥品及試劑 7 2-2 西方墨點法使用的一級抗體 9 2-3 西方墨點法使用的二級抗體 9 2-4 細胞培養 9 2-5 質體萃取(Midi Plus extract) 10 2-6 半定量反轉錄聚合酶連鎖反應(Semi-quantitative reverse-transcriptase polymerase chain reaction,簡稱Semi-q-PCR) 10 2-7西方墨點法(Western blot) 10 2-8 冷光素酶檢測法(Luciferase Reporter Assays) 11 2-9 細胞計數(Cell counting) 11 2-10 統計分析(Statistical analysis) 11 第三章 結果 12 3-1 SPZ1和BRAF表現與肝癌患者的性別無顯著差異 12 3-2 SPZ1表現與腫瘤期數和腫瘤大小具有顯著性 12 3-3 SPZ1與麩丙酮酸轉氨脢及淋巴血管侵犯具有顯著性 12 3-4 驗證SPZ1和BRAF表現量對於病人預後生存的預後準確性 13 3-5 高度表現SPZ1和BRAF對於病人有較差的預後 13 3-6 SPZ1和BRAF在肝癌的腫瘤組織上有高表現 13 3-7 SPZ1 mRNA表現與BRAF mRNA表現呈中度正相關 13 3-8 Huh 7和SK-Hep1細胞中的SPZ1轉染效率 13 3-9 SPZ1會促進BRAF mRNA表現量 14 3-10 SPZ1會促進細胞增生相關基因的mRNA表現量 14 3-11 肝癌細胞中shSPZ1降低SPZ1和BRAF蛋白質的表現量 14 3-12 SPZ1會活化BRAF啟動子 14 3-13 shBRAF會抑制BRAF蛋白質表現 15 3-14在Huh7細胞中SPZ1可能透過BRAF促進細胞增生 15 3-15在Huh7細胞中SPZ1可能透過BRAF促進細胞生長 15 第四章 討論 16 第五章 參考文獻 20 第六章 表 23 第七章 圖 28 第八章 附錄 41

    1. Bray, F., et al., Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018. 68(6): p. 394-424.
    2. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol, 2012. 56(4): p. 908-43.
    3. Moon, H. and S.W. Ro, MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma. Cancers (Basel), 2021. 13(12).
    4. Xu, C., et al., β-Catenin signaling in hepatocellular carcinoma. J Clin Invest, 2022. 132(4).
    5. Wang, L.T., et al., Transcription factor SPZ1 promotes TWIST-mediated epithelial-mesenchymal transition and oncogenesis in human liver cancer. Oncogene, 2017. 36(31): p. 4405-4414.
    6. Yang, J.D., et al., A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol, 2019. 16(10): p. 589-604.
    7. Bruix, J., L.G. da Fonseca, and M. Reig, Insights into the success and failure of systemic therapy for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol, 2019. 16(10): p. 617-630.
    8. Hsu, S.-H., et al., Spz1, a novel bHLH-Zip protein, is specifically expressed in testis. Mechanisms of Development, 2001. 100(2): p. 177-187.
    9. Hsu, S.H., et al., bHLH-zip transcription factor Spz1 mediates mitogen-activated protein kinase cell proliferation, transformation, and tumorigenesis. Cancer Res, 2005. 65(10): p. 4041-50.
    10. Hsu, S.H., H.M. Hsieh-Li, and H. Li, Dysfunctional spermatogenesis in transgenic mice overexpressing bHLH-Zip transcription factor, Spz1. Exp Cell Res, 2004. 294(1): p. 185-98.
    11. Liu, X.Y., et al., SPZ1 promotes deregulation of Bim to boost apoptosis resistance in colorectal cancer. Clin Sci (Lond), 2020. 134(2): p. 155-167.
    12. Wang, L.-T., et al., TIP60-dependent acetylation of the SPZ1-TWIST complex promotes epithelial–mesenchymal transition and metastasis in liver cancer. Oncogene, 2019. 38(4): p. 518-532.
    13. Liu, X., et al., SPZ1 is critical for chemoresistance and aggressiveness in drug-resistant breast cancer cells. Biochemical Pharmacology, 2018. 156: p. 43-51.
    14. Hsu, S.H., et al., Spz1, a novel bHLH-Zip protein, is specifically expressed in testis. Mech Dev, 2001. 100(2): p. 177-87.
    15. Di, C., et al., SPZ1 promotes glioma aggravation via targeting CXXC4. J buon, 2021. 26(2): p. 373-379.
    16. Beck, T.W., et al., The complete coding sequence of the human A-raf-1 oncogene and transforming activity of a human A-raf carrying retrovirus. Nucleic Acids Res, 1987. 15(2): p. 595-609.
    17. Ghosh, S. and R.M. Bell, Identification of discrete segments of human Raf-1 kinase critical for high affinity binding to Ha-Ras. J Biol Chem, 1994. 269(49): p. 30785-8.
    18. Mott, H.R., et al., The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site. Proc Natl Acad Sci U S A, 1996. 93(16): p. 8312-7.
    19. Scheffler, J.E., et al., Characterization of a 78-residue fragment of c-Raf-1 that comprises a minimal binding domain for the interaction with Ras-GTP. J Biol Chem, 1994. 269(35): p. 22340-6.
    20. Vojtek, A.B., S.M. Hollenberg, and J.A. Cooper, Mammalian Ras interacts directly with the serine/threonine kinase Raf. Cell, 1993. 74(1): p. 205-14.
    21. Daum, G., et al., The ins and outs of Raf kinases. Trends Biochem Sci, 1994. 19(11): p. 474-80.
    22. Morrison, D.K. and R.E. Cutler, The complexity of Raf-1 regulation. Curr Opin Cell Biol, 1997. 9(2): p. 174-9.
    23. Yi, Q., et al., Spectrum of BRAF Aberrations and Its Potential Clinical Implications: Insights From Integrative Pan-Cancer Analysis. Front Bioeng Biotechnol, 2022. 10: p. 806851.
    24. Zaman, A., W. Wu, and T.G. Bivona, Targeting Oncogenic BRAF: Past, Present, and Future. Cancers (Basel), 2019. 11(8).
    25. Subbiah, V., C. Baik, and J.M. Kirkwood, Clinical Development of BRAF plus MEK Inhibitor Combinations. Trends Cancer, 2020. 6(9): p. 797-810.
    26. Brtva, T.R., et al., Two Distinct Raf Domains Mediate Interaction with Ras (∗). Journal of Biological Chemistry, 1995. 270(17): p. 9809-9812.
    27. Hu, C.-D., et al., Cysteine-rich Region of Raf-1 Interacts with Activator Domain of Post-translationally Modified Ha-Ras (∗). Journal of Biological Chemistry, 1995. 270(51): p. 30274-30277.
    28. Marais, R., et al., Differential regulation of Raf-1, A-Raf, and B-Raf by oncogenic ras and tyrosine kinases. J Biol Chem, 1997. 272(7): p. 4378-83.
    29. Maurer, G., B. Tarkowski, and M. Baccarini, Raf kinases in cancer-roles and therapeutic opportunities. Oncogene, 2011. 30(32): p. 3477-88.
    30. Khan, P.S., et al., Recent advances in B-RAF inhibitors as anticancer agents. Bioorganic Chemistry, 2022. 120: p. 105597.
    31. Śmiech, M., et al., Oncogenic Mutation BRAF V600E Changes Phenotypic Behavior of THLE-2 Liver Cells through Alteration of Gene Expression. Int J Mol Sci, 2022. 23(3).
    32. Ito, Y., et al., Activation of mitogen-activated protein kinases/extracellular signal-regulated kinases in human hepatocellular carcinoma. Hepatology, 1998. 27(4): p. 951-8.
    33. Hoffmann, K., et al., Correlation of gene expression of ATP-binding cassette protein and tyrosine kinase signaling pathway in patients with hepatocellular carcinoma. Anticancer Res, 2011. 31(11): p. 3883-90.
    34. Zuo, Q., et al., Multivariate analysis of several molecular markers and clinicopathological features in postoperative prognosis of hepatocellular carcinoma. Anat Rec (Hoboken), 2012. 295(3): p. 423-31.
    35. Liu, L., et al., Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res, 2006. 66(24): p. 11851-8.
    36. Schmitz, K.J., et al., Activation of the ERK and AKT signalling pathway predicts poor prognosis in hepatocellular carcinoma and ERK activation in cancer tissue is associated with hepatitis C virus infection. J Hepatol, 2008. 48(1): p. 83-90.
    37. Meseure, D., et al., Long Noncoding RNAs as New Architects in Cancer Epigenetics, Prognostic Biomarkers, and Potential Therapeutic Targets. Biomed Res Int, 2015. 2015: p. 320214.
    38. Gnoni, A., et al., Role of BRAF in Hepatocellular Carcinoma: A Rationale for Future Targeted Cancer Therapies. Medicina (Kaunas), 2019. 55(12).
    39. Sathornsumetee, S., et al., AAL881, a novel small molecule inhibitor of RAF and vascular endothelial growth factor receptor activities, blocks the growth of malignant glioma. Cancer Res, 2006. 66(17): p. 8722-30.
    40. Wang, W., et al., Synergistic activity of magnolin combined with B-RAF inhibitor SB590885 in hepatocellular carcinoma cells via targeting PI3K-AKT/mTOR and ERK MAPK pathway. Am J Transl Res, 2019. 11(6): p. 3816-3824.
    41. Chidambaranathan-Reghupaty, S., P.B. Fisher, and D. Sarkar, Hepatocellular carcinoma (HCC): Epidemiology, etiology and molecular classification. Adv Cancer Res, 2021. 149: p. 1-61.
    42. Chakraborty, E. and D. Sarkar, Emerging Therapies for Hepatocellular Carcinoma (HCC). Cancers (Basel), 2022. 14(11).
    43. J.F. Lopez-Saezl, C.d.l.T., J. Pincheira and G. Gimbnez-Martin, Cell proliferation and cancer. Histology and Histo pathology, 1998. 13: p. 1197-1214.

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