探討硒代胱氨酸於神經母細胞瘤之治療潛力

以作者查詢圖書館館藏

、以作者查詢臺灣博碩士

、以作者查詢全國書目

、勘誤回報

、線上人數：99

、訪客IP：18.225.234.175

姓名

曾桾溦(Chun-Wei Tseng) 查詢紙本館藏

畢業系所

生命科學系

論文名稱

探討硒代胱氨酸於神經母細胞瘤之治療潛力
(The Therapeutic Potential of Selenocystine in Neuroblastoma)

相關論文

★ 探討化合物 Y 抑制神經母細胞瘤增生之效果	★ 探討化合物Y抑制神經母細胞瘤轉移之效果
★ 探討TIMP-3在EGFR抑制劑治療神經母細胞瘤中的調節機制

檔案

[Endnote RIS 格式]

[Bibtex 格式]

[相關文章]

[文章引用]

[完整記錄]

[館藏目錄]

至系統瀏覽論文 (2026-8-31以後開放)

摘要(中)

神經母細胞瘤（Neuroblastoma, NB）是一種源於交感神經系統胚胎神經嵴細胞的神經癌症，是兒童中最常見的顱外固體腫瘤。高風險患者通常高機率會有低生存率和不良的預後的狀況發生，因此想要提升高風險群體的存活率，開發有效的抗癌藥物是迫切需要的。硒代胱氨酸（Selenocystine, SeC）作為一種含硒氨基酸，已被許多先前的研究證實它是一個有抗腫瘤治療前景的候選藥物。更重要的是，SeC能夠選擇性地靶向癌細胞，而不對正常細胞造成損害。儘管在多種癌症類型中已經說明了SeC的抗增殖效應和其很適合做為抗癌藥物的選擇性，但SeC在NB中的治療潛力仍然鮮有研究。本研究旨在使用SK-N-BE(2)C和SK-N-SH細胞作為體外模型，探討SeC作為NB治療劑的功效。細胞計數、MTS試驗和聚落形成試驗顯示，SeC處理後細胞存活率呈劑量依賴性下降，突顯了其對NB的抗增殖效應。進一步使用流式細胞儀分析表明，SeC誘導細胞在Sub-G1期的積聚和Annexin V陽性細胞增加，表明細胞凋亡的發生。不論是對於凋亡相關的蛋白質標記如PARP、Caspase 3、Caspase 8和Bcl-2，還是對於凋亡相關的基因標記表達水平如Bcl-2和Bax，均顯示出明顯的凋亡效應。為了闡明其潛在機制，我們在SeC處理的SK-N-BE(2)C細胞中進行了RNA-Seq分析。從生物學過程（Biological Process, BP）和疾病本體（Disease Ontology, DO）的超表達分析中可以明顯看出，許多與神經功能相關的基因發生了改變。這進一步證實了SeC對NB細胞具有很大的影響。從Volcano Plot可以看出KLF4和CDKN1A基因明顯上調，顯示SeC誘導的細胞週期阻滯和細胞凋亡可能通過KLF4-CDKN1A途徑進行調節。隨後的研究將探討KLF4和CDKN1A在SeC誘導的NB細胞反應中的具體作用。除此之外，將進行體內腫瘤異種移植研究，以進一步驗證SeC在更貼近生理情況下的治療潛力。

摘要(英)

Neuroblastoma (NB) is a neural cancer originating from embryonic neural crest cells of the sympathetic nervous system. It represents the most prevalent extracranial solid tumor in children, and patients classified as high-risk typically face a poor prognosis with low survival rates. Developing an effective anti-tumor drug for high-risk patients is urgent for the current NB treatment. Selenocystine (SeC), a selenium-containing amino acid, has emerged as a promising candidate for anti-tumor therapy in several previous studies. Importantly, SeC can selectively target cancer cells while sparing normal cells from harm. Despite the documented anti-proliferative effects and the advantageous characteristic of SeC across various cancer types, its therapeutic potential in NB remains largely unexplored. In this study, we aim to investigate the efficacy of SeC as a therapeutic agent for NB using SK-N-BE(2)C and SK-N-SH cells as in-vitro models. Cell counting, MTS assays, and colony formation assays revealed a dose-dependent reduction in cell viability following SeC treatment, underscoring its anti-proliferative effects in NB. Further analysis using flow cytometry demonstrated SeC-induced accumulation of cells in the sub-G1 phase and an increase in Annexin V-positive cells, indicative of apoptosis. Regardless of the protein markers of apoptosis such as PARP, Caspase 3, Caspase 8, and Bcl-2, or the mRNAs expression levels of apoptosis-related genes such as Bcl-2 and Bax, both of them showed significant apoptosis induced by SeC. To elucidate the underlying mechanisms, RNA-Seq analysis was employed in SeC-treated SK-N-BE(2)C cells. From the over-representation analysis of Biological Process (BP) and Disease Ontology (DO), it is evident that numerous genes related to neural functions are altered. This further confirms that SeC has a huge impact on NB cells. The volcano plot revealed significant upregulation of the KLF4 and CDKN1A genes, indicating that SeC-induced cell cycle arrest and apoptosis in NB cells may be mediated by the KLF4-CDKN1A pathway. Subsequent studies will explore the specific roles of KLF4 and CDKN1A in SeC-induced responses in NB cells. Additionally, an in-vivo xenograft study will be conducted to validate the therapeutic potential of SeC in a more physiological setting.

關鍵字(中)

★ 神經母細胞瘤
★ 硒代胱氨酸

關鍵字(英)

★ Neuroblastoma
★ Selenocystine

論文目次

誌謝 i
中文摘要 ii
Abstract iii
Table of Contents v
List of Figures ix
List of Tables x
Chapter 1. Introduction - 1 -
1-1 Basic information of neuroblastoma - 1 -
1-1-1 Neuroblastoma - 1 -
1-1-2 MYCN is an important biomarker of NB - 2 -
1-2 Roles of KLF4 in neuroblastoma - 2 -
1-2-1 Characteristics of KLF4 - 3 -
1-2-2 Functions in KLF4 in cancers - 3 -
1-2-3 KLF4 signaling pathways in tumors - 4 -
1-2-4 KLF4 might be a tumor suppressor in NB - 5 -
1-3 Roles of CDKN1A in neuroblastoma - 6 -
1-3-1 Characteristics of CDKN1A - 6 -
1-3-2 Functions in CDKN1A in cancers - 6 -
1-3-3 CDKN1A might be a tumor suppressor in NB - 7 -
1-3-4 The connection between KLF4 and CDKN1A in NB - 8 -
1-4 Selenocystine (SeC) - 8 -
1-4-1 The function of selenium in the human - 8 -
1-4-2 Anticancer activities of selenocompounds - 8 -
1-4-3 Characteristic of Selenocystine in cancer cell - 9 -
1-5 Rationale - 11 -
1-6 Research framework - 12 -
Chapter 2. Materials & Methods - 13 -
2-1 Cell lines & medicament - 13 -
2-2 Cell culture - 13 -
2-3 MTS assay - 13 -
2-4 Cell counting - 14 -
2-5 qPCR - 15 -
2-5-1 RNA extraction - 15 -
2-5-2 Reverse transcription PCR (RT-PCR) - 16 -
2-5-3 Quantitate real-time PCR (qRT-PCR) - 16 -
2-6 Western blot - 17 -
2-6-1 Protein extraction - 17 -
2-6-2 SDS-polyacrylamide gel electrophoresis, SDS-PAGE - 17 -
2-6-3 Transfer - 18 -
2-6-4 Blocking and antibody recognition - 18 -
2-6-5 Stripping - 18 -
2-7 Flow cytometry - 19 -
2-7-1 Cell apoptosis assay - 19 -
2-7-2 Cell cycle distribution analysis - 19 -
2-8 Colony formation - 20 -
2-9 RNA-sequencing - 21 -
2-9-1 RNA QC - 21 -
2-9-2 Library Preparation and Sequencing - 21 -
2-9-3 Differential Expression Analysis - 21 -
2-9-4 Enrichment Analysis - 22 -
2-10 Statistical analysis - 22 -
Chapter 3. Results - 23 -
3-1 SeC inhibits the cell proliferation of NB cells - 23 -
3-2 SeC downregulates PCNA protein expression level and mRNA expression in NB cell lines - 24 -
3-3 SeC promotes the accumulation of NB cells in Sub-G1 phase - 24 -
3-4 SeC induces apoptosis of NB cells - 24 -
3-5 RNA sequencing analysis demonstrates the induction of KLF4 and CDKN1A in SeC-treated NB cells - 25 -
Chapter 4. Discussions & Conclusion - 27 -
Chapter 5. References - 32 -
Chapter 6. Appendixes - 63 -

參考文獻

1. Bagatell R, DuBois SG, Naranjo A, Belle J, Goldsmith KC, Park JR, Irwin MS, Committee CN: Children′s Oncology Group′s 2023 blueprint for research: Neuroblastoma. Pediatric Blood & Cancer 2023, 70:e30572.
2. Cheung N-KV, Dyer MA: Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Nature Reviews Cancer 2013, 13(6):397-411.
3. Wright JH: Neurocytoma or neuroblastoma, a kind of tumor not generally recognized. The Journal of experimental medicine 1910, 12(4):556.
4. Tsubota S, Kadomatsu K: Origin and initiation mechanisms of neuroblastoma. Cell and tissue research 2018, 372:211-221.
5. Park JR, Eggert A, Caron H: Neuroblastoma: biology, prognosis, and treatment. Pediatric Clinics of North America 2008, 55(1):97-120.
6. Pinto NR, Applebaum MA, Volchenboum SL, Matthay KK, London WB, Ambros PF, Nakagawara A, Berthold F, Schleiermacher G, Park JR: Advances in risk classification and treatment strategies for neuroblastoma. Journal of clinical oncology 2015, 33(27):3008.
7. Park JR, Bagatell R, London WB, Maris JM, Cohn SL, Mattay KM, Hogarty M, Committee CN: Children′s Oncology Group′s 2013 blueprint for research: neuroblastoma. Pediatric blood & cancer 2013, 60(6):985-993.
8. Cohn SL, Pearson AD, London WB, Monclair T, Ambros PF, Brodeur GM, Faldum A, Hero B, Iehara T, Machin D: The International Neuroblastoma Risk Group (INRG) classification system: an INRG task force report. Journal of clinical oncology 2009, 27(2):289.
9. Mueller S, Matthay KK: Neuroblastoma: biology and staging. Current oncology reports 2009, 11:431-438.
10. Liang WH, Federico SM, London WB, Naranjo A, Irwin MS, Volchenboum SL, Cohn SL: Tailoring therapy for children with neuroblastoma on the basis of risk group classification: past, present, and future. JCO Clinical Cancer Informatics 2020, 4:895-905.
11. Kohl NE, Kanda N, Schreck RR, Bruns G, Latt SA, Gilbert F, Alt FW: Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell 1983, 35(2):359-367.
12. Schwab M, Alitalo K, Klempnauer K-H, Varmus HE, Bishop JM, Gilbert F, Brodeur G, Goldstein M, Trent J: Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature 1983, 305(5931):245-248.
13. Knoepfler PS, Cheng PF, Eisenman RN: N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation. Genes & development 2002, 16(20):2699-2712.
14. Weiss WA, Aldape K, Mohapatra G, Feuerstein BG, Bishop JM: Targeted expression of MYCN causes neuroblastoma in transgenic mice. The EMBO journal 1997.
15. Huang M, Weiss WA: Neuroblastoma and MYCN. Cold Spring Harbor perspectives in medicine 2013, 3(10):a014415.
16. Chen L, Iraci N, Gherardi S, Gamble LD, Wood KM, Perini G, Lunec J, Tweddle DA: p53 is a direct transcriptional target of MYCN in neuroblastoma. Cancer research 2010, 70(4):1377-1388.
17. Slack A, Chen Z, Tonelli R, Pule M, Hunt L, Pession A, Shohet JM: The p53 regulatory gene MDM2 is a direct transcriptional target of MYCN in neuroblastoma. Proceedings of the National Academy of Sciences 2005, 102(3):731-736.
18. Selmi A, de Saint-Jean M, Jallas A-C, Garin E, Hogarty MD, Bénard J, Puisieux A, Marabelle A, Valsesia-Wittmann S: TWIST1 is a direct transcriptional target of MYCN and MYC in neuroblastoma. Cancer letters 2015, 357(1):412-418.
19. Evans L, Chen L, Milazzo G, Gherardi S, Perini G, Willmore E, Newell DR, Tweddle DA: SKP2 is a direct transcriptional target of MYCN and a potential therapeutic target in neuroblastoma. Cancer letters 2015, 363(1):37-45.
20. Gupta A, Williams BR, Hanash SM, Rawwas J: Cellular Retinoic Acid–Binding Protein II Is a Direct Transcriptional Target of MycN in Neuroblastoma. Cancer research 2006, 66(16):8100-8108.
21. Marshall GM, Gherardi S, Xu N, Neiron Z, Trahair T, Scarlett C, Chang DK, Liu PY, Jankowski K, Iraci N: Transcriptional upregulation of histone deacetylase 2 promotes Myc-induced oncogenic effects. Oncogene 2010, 29(44):5957-5968.
22. Iraci N, Diolaiti D, Papa A, Porro A, Valli E, Gherardi S, Herold S, Eilers M, Bernardoni R, Valle GD: A SP1/MIZ1/MYCN repression complex recruits HDAC1 at the TRKA and p75NTR promoters and affects neuroblastoma malignancy by inhibiting the cell response to NGF. Cancer research 2011, 71(2):404-412.
23. Ling H, Fabbri M, Calin GA: MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nature reviews Drug discovery 2013, 12(11):847-865.
24. Tang XX, Zhao H, Kung B, Kim DY, Hicks SL, Cohn SL, Cheung N-K, Seeger RC, Evans AE, Ikegaki N: The MYCN enigma: significance of MYCN expression in neuroblastoma. Cancer research 2006, 66(5):2826-2833.
25. Tetreault M-P, Yang Y, Katz JP: Krüppel-like factors in cancer. Nature Reviews Cancer 2013, 13(10):701-713.
26. Aksoy I, Giudice V, Delahaye E, Wianny F, Aubry M, Mure M, Chen J, Jauch R, Bogu GK, Nolden T: Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells. Nature communications 2014, 5(1):3719.
27. Shields JM, Yang VW: Two potent nuclear localization signals in the gut-enriched Krüppel-like factor define a subfamily of closely related Krüppel proteins. Journal of Biological Chemistry 1997, 272(29):18504-18507.
28. Song A, Patel A, Thamatrakoln K, Liu C, Feng D, Clayberger C, Krensky AM: Functional domains and DNA-binding sequences of RFLAT-1/KLF13, a Krüppel-like transcription factor of activated T lymphocytes. Journal of Biological Chemistry 2002, 277(33):30055-30065.
29. Zhu Y, Wu D, Wang M, Li W: C-terminus of E1A binding protein 1 stimulates malignant phenotype in human hepatocellular carcinoma. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research 2019, 25:8660.
30. Adams MK, Banks CA, Thornton JL, Kempf CG, Zhang Y, Miah S, Hao Y, Sardiu ME, Killer M, Hattem GL: Differential complex formation via paralogs in the human Sin3 protein interaction network. Molecular & Cellular Proteomics 2020, 19(9):1468-1484.
31. Piskacek M, Havelka M, Jendruchova K, Knight A, Keegan LP: The evolution of the 9aaTAD domain in Sp2 proteins: inactivation with valines and intron reservoirs. Cellular and molecular life sciences 2020, 77:1793-1810.
32. Schuetz A, Nana D, Rose C, Zocher G, Milanovic M, Koenigsmann J, Blasig R, Heinemann U, Carstanjen D: The structure of the Klf4 DNA-binding domain links to self-renewal and macrophage differentiation. Cellular and Molecular Life Sciences 2011, 68:3121-3131.
33. Shields JM, Christy RJ, Yang VW: Identification and characterization of a gene encoding a gut-enriched Krüppel-like factor expressed during growth arrest. Journal of Biological Chemistry 1996, 271(33):20009-20017.
34. He Z, He J, Xie K: KLF4 transcription factor in tumorigenesis. Cell Death Discovery 2023, 9(1):118.
35. Yu T, Chen X, Zhang W, Liu J, Avdiushko R, Napier D, Liu A, Neltner J, Wang C, Cohen D: KLF4 regulates adult lung tumor-initiating cells and represses K-Ras-mediated lung cancer. Cell Death & Differentiation 2016, 23(2):207-215.
36. Wang J, Place RF, Huang V, Wang X, Noonan EJ, Magyar CE, Huang J, Li L-C: Prognostic value and function of KLF4 in prostate cancer: RNAa and vector-mediated overexpression identify KLF4 as an inhibitor of tumor cell growth and migration. Cancer research 2010, 70(24):10182-10191.
37. Siu M, Suau F, Chen W, Tsai Y, Tsai H, Yeh H, Liu Y: KLF4 functions as an activator of the androgen receptor through reciprocal feedback. Oncogenesis 2016, 5(12):e282-e282.
38. Garrett-Sinha LA, Eberspaecher H, Seldin MF, de Crombrugghe B: A gene for a novel zinc-finger protein expressed in differentiated epithelial cells and transiently in certain mesenchymal cells. Journal of Biological Chemistry 1996, 271(49):31384-31390.
39. Yang VW, Liu Y, Kim J, Shroyer KR, Bialkowska AB: Increased genetic instability and accelerated progression of colitis-associated colorectal cancer through intestinal epithelium–specific deletion of Klf4. Molecular Cancer Research 2019, 17(1):165-176.
40. Yu F, Li J, Chen H, Fu J, Ray S, Huang S, Zheng H, Ai W: Kruppel-like factor 4 (KLF4) is required for maintenance of breast cancer stem cells and for cell migration and invasion. Oncogene 2011, 30(18):2161-2172.
41. Riverso M, Montagnani V, Stecca B: KLF4 is regulated by RAS/RAF/MEK/ERK signaling through E2F1 and promotes melanoma cell growth. Oncogene 2017, 36(23):3322-3333.
42. Wei D, Wang L, Yan Y, Jia Z, Gagea M, Li Z, Zuo X, Kong X, Huang S, Xie K: KLF4 is essential for induction of cellular identity change and acinar-to-ductal reprogramming during early pancreatic carcinogenesis. Cancer cell 2016, 29(3):324-338.
43. Prasad NB, Biankin AV, Fukushima N, Maitra A, Dhara S, Elkahloun AG, Hruban RH, Goggins M, Leach SD: Gene expression profiles in pancreatic intraepithelial neoplasia reflect the effects of Hedgehog signaling on pancreatic ductal epithelial cells. Cancer research 2005, 65(5):1619-1626.
44. Liu M, Li X, Peng K-Z, Gao T, Cui Y, Ma N, Zhou Y, Hou G: Subcellular localization of Klf4 in non-small cell lung cancer and its clinical significance. Biomedicine & pharmacotherapy 2018, 99:480-485.
45. Taracha-Wisniewska A, Kotarba G, Dworkin S, Wilanowski T: Recent discoveries on the involvement of Krüppel-like factor 4 in the most common cancer types. International Journal of Molecular Sciences 2020, 21(22):8843.
46. Wei D, Kanai M, Jia Z, Le X, Xie K: Kruppel-like factor 4 induces p27Kip1 expression in and suppresses the growth and metastasis of human pancreatic cancer cells. Cancer research 2008, 68(12):4631-4639.
47. Yan Y, Li Z, Kong X, Jia Z, Zuo X, Gagea M, Huang S, Wei D, Xie K: KLF4-mediated suppression of CD44 signaling negatively impacts pancreatic cancer stemness and metastasis. Cancer research 2016, 76(8):2419-2431.
48. Zhu Z, Yu Z, Wang J, Zhou L, Zhang J, Yao B, Dou J, Qiu Z, Huang C: Krüppel-like factor 4 inhibits pancreatic cancer epithelial-to-mesenchymal transition and metastasis by down-regulating caveolin-1 expression. Cellular Physiology and Biochemistry 2018, 46(1):238-252.
49. Guo K, Cui J, Quan M, Xie D, Jia Z, Wei D, Wang L, Gao Y, Ma Q, Xie K: The novel KLF4/MSI2 signaling pathway regulates growth and metastasis of pancreatic cancer. Clinical Cancer Research 2017, 23(3):687-696.
50. Kong X, Li L, Li Z, Le X, Huang C, Jia Z, Cui J, Huang S, Wang L, Xie K: Dysregulated expression of FOXM1 isoforms drives progression of pancreatic cancer. Cancer research 2013, 73(13):3987-3996.
51. Shi M, Cui J, Du J, Wei D, Jia Z, Zhang J, Zhu Z, Gao Y, Xie K: A novel KLF4/LDHA signaling pathway regulates aerobic glycolysis in and progression of pancreatic cancer. Clinical Cancer Research 2014, 20(16):4370-4380.
52. Wei D, Kanai M, Huang S, Xie K: Emerging role of KLF4 in human gastrointestinal cancer. Carcinogenesis 2005, 27(1):23-31.
53. Ghaleb AM, Yang VW: Krüppel-like factor 4 (KLF4): What we currently know. Gene 2017, 611:27-37.
54. Shum C, Lau S, Tsoi L, Chan L, Yam J, Ohira M, Nakagawara A, Tam P, Ngan E: Krüppel-like factor 4 (KLF4) suppresses neuroblastoma cell growth and determines non-tumorigenic lineage differentiation. Oncogene 2013, 32(35):4086-4099.
55. Ray SK: The transcription regulator Kruppel-like factor 4 and its dual roles of oncogene in glioblastoma and tumor suppressor in neuroblastoma. Onco Therapeutics 2016, 7(1-2).
56. Mohan N, Ai W, Chakrabarti M, Banik NL, Ray SK: KLF4 overexpression and apigenin treatment down regulated anti-apoptotic Bcl-2 proteins and matrix metalloproteinases to control growth of human malignant neuroblastoma SK-N-DZ and IMR-32 cells. Molecular oncology 2013, 7(3):464-474.
57. Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D: p21 is a universal inhibitor of cyclin kinases. Nature 1993, 366(6456):701-704.
58. Abbas T, Dutta A: p21 in cancer: intricate networks and multiple activities. Nature Reviews Cancer 2009, 9(6):400-414.
59. Kreis N, Louwen F, Yuan J: Less understood issues: p21Cip1 in mitosis and its therapeutic potential. Oncogene 2015, 34(14):1758-1767.
60. Roninson IB: Oncogenic functions of tumour suppressor p21Waf1/Cip1/Sdi1: association with cell senescence and tumour-promoting activities of stromal fibroblasts. Cancer letters 2002, 179(1):1-14.
61. Follis AV, Galea CA, Kriwacki RW: Intrinsic protein flexibility in regulation of cell proliferation: advantages for signaling and opportunities for novel therapeutics. Fuzziness: Structural Disorder in Protein Complexes 2012:27-49.
62. El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B: WAF1, a potential mediator of p53 tumor suppression. Cell 1993, 75(4):817-825.
63. Besson A, Dowdy SF, Roberts JM: CDK inhibitors: cell cycle regulators and beyond. Developmental cell 2008, 14(2):159-169.
64. LaBaer J, Garrett MD, Stevenson LF, Slingerland JM, Sandhu C, Chou HS, Fattaey A, Harlow E: New functional activities for the p21 family of CDK inhibitors. Genes & development 1997, 11(7):847-862.
65. Dash BC, El-Deiry WS: Phosphorylation of p21 in G2/M promotes cyclin B-Cdc2 kinase activity. Molecular and cellular biology 2005.
66. Gartel AL, Tyner AL: Transcriptional regulation of the p21 (WAF1/CIP1) gene. Experimental cell research 1999, 246(2):280-289.
67. Mitchell KO, El-Deiry WS: Overexpression of c-Myc inhibits p21WAF1/CIP1 expression and induces S-phase entry in 12-O-tetradecanoylphorbol-13-acetate (TPA)-sensitive human cancer cells. 1999.
68. Kitaura H, Shinshi M, Uchikoshi Y, Ono T, Tsurimoto T, Yoshikawa H, Iguchi-Ariga SM, Ariga H: Reciprocal regulation via protein-protein interaction between c-Myc and p21 cip1/waf1/sdi1 in DNA replication and transcription. Journal of Biological Chemistry 2000, 275(14):10477-10483.
69. Waga S, Hannon GJ, Beach D, Stillman B: The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 1994, 369(6481):574-578.
70. Engeland K: Cell cycle arrest through indirect transcriptional repression by p53: I have a DREAM. Cell Death & Differentiation 2018, 25(1):114-132.
71. Chang B-D, Watanabe K, Broude EV, Fang J, Poole JC, Kalinichenko TV, Roninson IB: Effects of p21Waf1/Cip1/Sdi1 on cellular gene expression: implications for carcinogenesis, senescence, and age-related diseases. Proceedings of the National Academy of Sciences 2000, 97(8):4291-4296.
72. Teramen H, Tsukuda K, Tanaka N, Ueno T, Kubo T, Ando M, Soh J, Asano H, Pass HI, Toyooka S: Aberrant methylation of p21 gene in lung cancer and malignant pleural mesothelioma. Acta Medica Okayama 2011, 65(3):179-184.
73. Bott S, Arya M, Kirby R, Williamson M: p21WAF1/CIP1 gene is inactivated in metastatic prostatic cancer cell lines by promoter methylation. Prostate cancer and prostatic diseases 2005, 8(4):321-326.
74. Askari M, Sobti RC, Nikbakht M, Sharma SC: Aberrant promoter hypermethylation of p21 (WAF1/CIP1) gene and its impact on expression and role of polymorphism in the risk of breast cancer. Molecular and cellular biochemistry 2013, 382:19-26.
75. Roman-Gomez J, Castillejo JA, Jimenez A, Gonzalez MG, Moreno F, Rodriguez MdC, Barrios M, Maldonado J, Torres A: 5′ CpG island hypermethylation is associated with transcriptional silencing of the p21CIP1/WAF1/SDI1 gene and confers poor prognosis in acute lymphoblastic leukemia. Blood, The Journal of the American Society of Hematology 2002, 99(7):2291-2296.
76. Liu R, Wettersten HI, Park S-H, Weiss RH: Small-molecule inhibitors of p21 as novel therapeutics for chemotherapy-resistant kidney cancer. Future medicinal chemistry 2013, 5(9):991-994.
77. Tanaka T, Slamon DJ, Shimada H, Shimoda H, Fujisawa T, Ida N, Seeger RC: A significant association of Ha‐ras p21 in neuroblastoma cells with patient prognosis. A retrospective study of 103 cases. Cancer 1991, 68(6):1296-1302.
78. Seçme M, Eroğlu C, Dodurga Y, Bağcı G: Investigation of anticancer mechanism of oleuropein via cell cycle and apoptotic pathways in SH-SY5Y neuroblastoma cells. Gene 2016, 585(1):93-99.
79. Torkin R, Lavoie J-F, Kaplan DR, Yeger H: Induction of caspase-dependent, p53-mediated apoptosis by apigenin in human neuroblastoma. Molecular cancer therapeutics 2005, 4(1):1-11.
80. Yoon HS, Chen X, Yang VW: Krüppel-like factor 4 mediates p53-dependent G1/S cell cycle arrest in response to DNA damage. Journal of Biological Chemistry 2003, 278(4):2101-2105.
81. Chen X, Johns DC, Geiman DE, Marban E, Dang DT, Hamlin G, Sun R, Yang VW: Krüppel-like factor 4 (gut-enriched Krüppel-like factor) inhibits cell proliferation by blocking G1/S progression of the cell cycle. Journal of Biological Chemistry 2001, 276(32):30423-30428.
82. Rowland BD, Bernards R, Peeper DS: The KLF4 tumour suppressor is a transcriptional repressor of p53 that acts as a context-dependent oncogene. Nature cell biology 2005, 7(11):1074-1082.
83. Rowland BD, Peeper DS: KLF4, p21 and context-dependent opposing forces in cancer. Nature Reviews Cancer 2006, 6(1):11-23.
84. Stadtman TC: Selenocysteine. Annual review of biochemistry 1996, 65(1):83-100.
85. Björnstedt M, Kumar S, Björkhem L, Spyrou G, Holmgren A: Selenium and the thioredoxin and glutaredoxin systems. Biomedical and environmental sciences: BES 1997, 10(2-3):271-279.
86. Rayman MP: The importance of selenium to human health. The lancet 2000, 356(9225):233-241.
87. Tapiero H, Townsend D, Tew K: The antioxidant role of selenium and seleno-compounds. Biomedicine & pharmacotherapy 2003, 57(3-4):134-144.
88. El-Bayoumy K, Sinha R: Mechanisms of mammary cancer chemoprevention by organoselenium compounds. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 2004, 551(1-2):181-197.
89. Sinha R, El-Bayoumy K: Apoptosis is a critical cellular event in cancer chemoprevention and chemotherapy by selenium compounds. Current cancer drug targets 2004, 4(1):13-28.
90. Chen T, Zheng W, Wong Y-S, Yang F: Mitochondria-mediated apoptosis in human breast carcinoma MCF-7 cells induced by a novel selenadiazole derivative. Biomedicine & pharmacotherapy 2008, 62(2):77-84.
91. Clark LC, Combs GF, Turnbull BW, Slate EH, Chalker DK, Chow J, Davis LS, Glover RA, Graham GF, Gross EG: Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: a randomized controlled trial. Jama 1996, 276(24):1957-1963.
92. Yu Yu S, Zhu YJ, Li WG: Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong. Biological trace element research 1997, 56:117-124.
93. Abdulah R, Miyazaki K, Nakazawa M, Koyama H: Chemical forms of selenium for cancer prevention. Journal of Trace Elements in Medicine and Biology 2005, 19(2-3):141-150.
94. Whanger P: Selenium and its relationship to cancer: an update. British journal of nutrition 2004, 91(1):11-28.
95. Zhao R, Xiang N, Domann FE, Zhong W: Expression of p53 enhances selenite-induced superoxide production and apoptosis in human prostate cancer cells. Cancer research 2006, 66(4):2296-2304.
96. F Jr CG: Current evidence and research needs to support a health claim for selenium and cancer prevention. The Journal of Nutrition 2005, 135(2):343-347.
97. Wang Z, Jiang C, Lü J: Induction of caspase‐mediated apoptosis and cell‐cycle G1 arrest by selenium metabolite methylselenol. Molecular Carcinogenesis: Published in cooperation with the University of Texas MD Anderson Cancer Center 2002, 34(3):113-120.
98. Lanfear J, Fleming J, Wu L, Webster G, Harrison PR: The selenium metabolite selenodiglutathione induces p53 and apoptosis: relevance to the chemopreventive effects of selenium? Carcinogenesis 1994, 15(7):1387-1392.
99. Sanmartín C, Plano D, Sharma AK, Palop JA: Selenium compounds, apoptosis and other types of cell death: an overview for cancer therapy. International journal of molecular sciences 2012, 13(8):9649-9672.
100. Fernandes AP, Gandin V: Selenium compounds as therapeutic agents in cancer. Biochimica et Biophysica Acta (BBA)-General Subjects 2015, 1850(8):1642-1660.
101. Chen T, Wong Y-S: Selenocystine induces reactive oxygen species–mediated apoptosis in human cancer cells. Biomedicine & Pharmacotherapy 2009, 63(2):105-113.
102. Chen T, Wong Y-S: Selenocystine induces caspase-independent apoptosis in MCF-7 human breast carcinoma cells with involvement of p53 phosphorylation and reactive oxygen species generation. The international journal of biochemistry & cell biology 2009, 41(3):666-676.
103. Chen T, Wong Y: Selenocystine induces apoptosis of A375 human melanoma cells by activating ROS-mediated mitochondrial pathway and p53 phosphorylation. Cellular and molecular life sciences 2008, 65:2763-2775.
104. Wahyuni EA, Yii C-Y, Liang H-L, Luo Y-H, Yang S-H, Wu P-Y, Hsu W-L, Nien C-Y, Chen S-C: Selenocystine induces oxidative-mediated DNA damage via impairing homologous recombination repair of DNA double-strand breaks in human hepatoma cells. Chemico-Biological Interactions 2022, 365:110046.
105. Fan C, Chen J, Wang Y, Wong Y-S, Zhang Y, Zheng W, Cao W, Chen T: Selenocystine potentiates cancer cell apoptosis induced by 5-fluorouracil by triggering reactive oxygen species-mediated DNA damage and inactivation of the ERK pathway. Free Radical Biology and Medicine 2013, 65:305-316.
106. Fan C, Zheng W, Fu X, Li X, Wong Y-S, Chen T: Strategy to enhance the therapeutic effect of doxorubicin in human hepatocellular carcinoma by selenocystine, a synergistic agent that regulates the ROS-mediated signaling. Oncotarget 2014, 5(9):2853.
107. Anders S: Analysing RNA-Seq data with the DESeq package. Mol Biol 2010, 43(4):1-17.
108. Love MI, Huber W, Anders S: Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome biology 2014, 15:1-21.
109. Yu G: Statistical analysis and visualization of functional profiles for genes and gene clusters. J Integr Biol 2012, 16(5):284-287.
110. Fan C-d, Fu X-y, Zhang Z-y, Cao M-z, Sun J-y, Yang M-f, Fu X-t, Zhao S-j, Shao L-r, Zhang H-f: Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk. Scientific Reports 2017, 7(1):6465.
111. Long M, Wu J, Hao J, Liu W, Tang Y, Li X, Su H, Qiu W: Selenocystine-induced cell apoptosis and S-phase arrest inhibit human triple-negative breast cancer cell proliferation. In Vitro Cellular & Developmental Biology-Animal 2015, 51:1077-1084.
112. Shimada H, Chatten J, Newton WA, Sachs N, Hamoudi AB, Chiba T, Marsden HB, Misugi K: Histopathologic prognostic factors in neuroblastic tumors: definition of subtypes of ganglioneuroblastoma and an age-linked classification of neuroblastomas. JNCI: Journal of the National Cancer Institute 1984, 73(2):405-416.
113. Walton JD, Kattan DR, Thomas SK, Spengler BA, Guo H-F, Biedler JL, Cheung N-KV, Ross RA: Characteristics of stem cells from human neuroblastoma cell lines and in tumors. Neoplasia 2004, 6(6):838-845.
114. Spengler BA, Lazarova DL, Ross RA, Biedler JL: Cell lineage and differentiation state are primary determinants of MYCN gene expression and malignant potential in human neuroblastoma cells. Oncology research 1997, 9(9):467-476.

指導教授

吳沛翊(Pei-Yi Wu)

審核日期

2024-8-22

推文