English  |  正體中文  |  简体中文  |  全文筆數/總筆數 : 45422/58598 (78%)
造訪人次 : 2532359      線上人數 : 238
RC Version 7.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜尋範圍 查詢小技巧：
  • 您可在西文檢索詞彙前後加上"雙引號"，以獲取較精準的檢索結果
  • 若欲以作者姓名搜尋，建議至進階搜尋限定作者欄位，可獲得較完整資料
    •  進階搜尋


    請使用永久網址來引用或連結此文件: http://libir.tmu.edu.tw/handle/987654321/59370


    題名: 亞甲基四氫葉酸脫氫酶(MTHFD2)向下調控對肺癌癌幹細胞特性之機制探討
    Down-regulation of MTHFD2 Expression Reduces Cancer Stem Cell Properties in Lung Cancer
    作者: 黃紹倫
    Huang, Hsao-Lun
    貢獻者: 生醫材料暨組織工程研究所
    鄧文炳
    關鍵詞: 亞甲基四氫葉酸脫氫酶;肺癌;癌幹細胞
    MTHFD2;Lung Cancer;Cancer Stem Cell
    日期: 2015-06-29
    上傳時間: 2020-08-19 13:53:10 (UTC+8)
    摘要: 在腫瘤組織中，存在著一小群具有自我再生及分化的細胞，稱之為癌症幹細胞。通常非原位腫瘤的發生或是癌細胞之轉移至也被認為與癌症幹細胞的特性有關。並且在細胞代謝途徑中被證實參與了癌症幹細胞與腫瘤的生成，例如糖解作用。亞甲基四氫葉酸脫氫酶(MTHFD2)為一個糖解作用中，調控單碳循環代謝之基因，亞甲基四氫葉酸脫氫酶能以絲氨酸及苷胺酸為單碳提供者，控制下游葉酸代謝循環合成核苷酸等大分子營養物質。在過去文獻發現可藉由亞甲基四氫葉酸脫氫酶調控癌細胞的生長，其調控機制與單碳循環的代謝有關，然而卻鮮少對於單碳循環中的致癌機制與癌症幹細胞做更詳細的討論。因此在本論文中則是欲得知是否亞甲基四氫葉酸脫氫酶可以藉由調控癌症代謝之機制進而影響癌症幹細胞在肺癌中的生成及特性。

    利用小片段RNA干擾抑制A549、H1299、H441三株非小細胞肺癌細胞中亞甲基四氫葉酸脫氫酶之表現，活體外測試中可以發現在細胞增生因亞甲基四氫葉酸脫氫酶的抑制而下降，呼應了過去文獻的結果，而同樣地在非貼附型軟瓊膠的群落(colony formation)生成能力測試中也發現細胞群落有被抑制的現象，並利用細胞球體試驗(sphere formation)以懸浮培養的方式誘導一般癌細胞轉變成具有癌幹細胞特性的型態，發現亞甲基四氫葉酸脫氫酶表現的抑制也可以減少細胞球體(sphere)的生成。然而我們利用外源性絲氨酸(serine)及苷胺酸(glycine)加入培養基後，於細胞增生與細胞球體實驗中皆發現了經過shMTHFD2干擾的組別中，抑制了由於外加絲氨酸及苷胺酸所促進的細胞增生及細胞球體數量，最後也發現這樣的現象可以是由三種癌症幹細胞標記基因調控有關，分別為ABCG2、CD133、CD166。因此於實驗結果中確實可以發現亞甲基四氫葉酸脫氫酶可以藉由碳循環代謝之調控，抑制非小細胞肺癌的細胞增生及癌症幹細胞之特性。
    Cancer stem cells (CSCs) are a subpopulation of tumor cells endowed with self-renewal and differentiation capacity. They are considered as a mainly cause of tumor recurrence and metastasis. Besides, not only aerobic glycolysis but several metabolic genes have been shown to affect CSC properties. Methylene-tetrahydrofolate dehydrogenase 2 (MTHFD2) which is participating in the one-carbon cycle for Ser/Gly metabolism in glycolysis and purine synthesis pathway has been revealed to contribute to cancer cell proliferation. Hence, this study aimed to investigate the mechanisms involved in the regulation of CSCs by MTHFD2.

    We used shRNA to down-regulate the expression of MTHFD2 in three NSCLC cell lines, including A549, H1299, and H441. All three NSCLC cells showed reduced growth ability, including cell proliferation and anchorage independent growth, upon knockdown of MTHFD2. In addition, we found that reduced MTHFD2 expression inhibits the tumor sphere formation of lung cancer cells, suggesting that MTHFD2 may contribute to the properties of lung cancer CSCs. To confirm the functional role of MTHFD2 in one-carbon metabolism associated with the malignant characteristics of cancer cells, we conducted cell proliferation and sphere formation assays by adding exogenous serine and glycine. The results showed that exogenous serine enhances the growth and initiation abilities of lung cancer cells, whereas the knockdown of MTHFD2 diminishes serine-induced enhancement. Real-time PCR further revealed that exogenous serine raises the expression of CSC markers, including ABCG2, CD133, and CD166, and these up-regulated genes can also be abolished by reducing MTHFD2 expression. In summary, current results indicate that MTHFD2 facilitates the CSC properties of lung cancer by mediating serine metabolism in one-carbon metabolic pathway.
    描述: 碩士
    指導教授:鄧文炳
    委員:何元順
    委員:吳駿翃
    資料類型: thesis
    顯示於類別:[生醫材料暨組織工程研究所] 博碩士論文

    文件中的檔案:

    檔案 描述 大小格式瀏覽次數
    index.html0KbHTML150檢視/開啟


    檢視Licence

    在TMUIR中所有的資料項目都受到原著作權保護.

    TAIR相關文章

    著作權聲明 Copyright Notice

    • 本平台之數位內容為臺北醫學大學所收錄之機構典藏，包含體系內各式學術著作及學術產出。秉持開放取用的精神，提供使用者進行資料檢索、下載與取用，惟仍請適度、合理地於合法範圍內使用本平台之內容，以尊重著作權人之權益。商業上之利用，請先取得著作權人之授權。

      The digital content on this platform is part of the Taipei Medical University Institutional Repository, featuring various academic works and outputs from the institution. It offers free access to academic research and public education for non-commercial use. Please use the content appropriately and within legal boundaries to respect copyright owners' rights. For commercial use, please obtain prior authorization from the copyright owner.

    • 瀏覽或使用本平台，視同使用者已完全接受並瞭解聲明中所有規範、中華民國相關法規、一切國際網路規定及使用慣例，並不得為任何不法目的使用TMUIR。

      By utilising the platform, users are deemed to have fully accepted and understood all the regulations set out in the statement, relevant laws of the Republic of China, all international internet regulations, and usage conventions. Furthermore, users must not use TMUIR for any illegal purposes.

    • 本平台盡力防止侵害著作權人之權益。若發現本平台之數位內容有侵害著作權人權益情事者，煩請權利人通知本平台維護人員([email protected])，將立即採取移除該數位著作等補救措施。

      TMUIR is made to protect the interests of copyright owners. If you believe that any material on the website infringes copyright, please contact our staff([email protected]). We will remove the work from the repository.

    Back to Top
    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - 回饋