探討miR-567在黑色素細胞瘤中的調控機制

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：40

、訪客IP：18.118.0.236

姓名

黃昱齊(Yu Chi Huang) 查詢紙本館藏

畢業系所

系統生物與生物資訊研究所

論文名稱

探討miR-567在黑色素細胞瘤中的調控機制
(Study of the mechanism of miR-567 in melanoma)

相關論文

★ 探討牛樟芝CCM111對細胞訊息傳遞之影響	★ Tyloxapol 在大腸癌細胞中的特異性及作用機制之研究
★ MAPK傳導路徑相關微型RNA在黑色素瘤細胞中功能之研究	★ 利用MAPK訊息傳導路徑相關的miRNAs來治療BRAF抑制劑的抗藥性在黑色素瘤細胞中之研究
★ 探索微型核糖核酸與慢性腎臟病及血液透析病人泌尿道上皮癌生物標記的相關性	★ 以miRNA為基礎開發偵測放射線治療抗性及預後的生物標記
★ 偵測微型核糖核酸 miR-524-5p表現量利用原位雜交染色法來作為輔助診斷惡性黑色素瘤的生物標記之研究	★ 研究牛樟芝萃取物 CCM111 的作用機制
★ 探討黑色素腫瘤中p53調控miR-524-5p及miR-596表現之機制	★ 泌尿道上皮癌相關的miRNAs在膀胱癌之研究
★ 探討BRAF抑制劑透過細胞間訊息誘導腫瘤形成之研究	★ 微型核糖核酸成為放射線治療的預後生物標記之研究
★ 發展以血中微型 RNA 作為冠心症(CAD)的非侵入性疾病指標	★ microRNAs作為放射治療預後之生物標誌物與miR-148a-3p於頭頸癌放射敏感度之研究
★ 研究miR-524-5p和miR-567治療在黑色素瘤與BRAF抑製劑的抗藥性黑色素瘤	★ 包覆性腹膜硬化症相關miRNAs在腹膜纖維化之研究

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 ( 永不開放)

摘要(中)

過去實驗室致力於探討Mitogen-Activated Protein Kinases/ Extracellular signal-Regulated Kinase (MAPK)訊息傳導路徑相關之微型核糖核酸 (miRNA)。在目前已知此訊息傳導路徑因突變而過度活化的黑色素細胞瘤 (melanoma) 中，發現諸多miRNA的過量表現 (overexpression) 均具有影響癌症相關細胞功能性能力，如增生(Proliferation)、遷移/侵襲 (Migration/Invasion)、凋亡 (Apoptosis)，認為此群miRNA具有癌症抑制基因(Tumor suppressor gene)之特質，並藉由抑制黑色素細胞瘤中可能產生預後不良的風險因子以及影響諸多與癌症進展相關之重要基因，希望將來成為有潛力的標靶治療手段。

摘要(英)

We dedicated to investigating Mitogen-Activated Protein Kinases/ Extracellular signal-Regulated Kinase (MAPK) pathway-associated miRNAs in our previous study. While these miRNAs are overexpressed, it could suppress the multiple functional assays related to cancer development, such as proliferation, migration, invasion, and apoptosis in melanoma which harbored the mutation(s) to make MAPK pathway active. We hope that these miRNAs play the meaningful role as tumor suppressors and they could become the promising RNA interference drug against the specific cancer.

關鍵字(中)

★ 微型核糖核酸
★ 黑色素細胞瘤

關鍵字(英)

★ miR-567
★ melanoma

論文目次

摘要 1
ABSTRACT 2
誌謝　　　　　　 3
List of figures 7
List of tables 7
Abbreviation list 8
Introduction 1
Disease 1
Cancer 1
Cutaneous melanoma 1
Genetic aberration in cutaneous melanoma 2
miRNA 5
Biological background 5
miRNA in gene expression regulation 6
Function of miRNA-RISC 6
how miRNA responds to mRNA, the miRNA recognition element 7
miRNA dysregulation 7
miRNA dysregulation and disease 7
miRNA in application and therapeutics 8
miR-567 9
Purpose and Significance 10
Materials and Methods 11
Cell line models 11
microRNA mimics preparation 11
Drugs and Reagents 12
Antibodies 12
miRNA transfection 12
Plasmid constructions, cloning, and mutagenesis 13
Preparation of lysate sample 13
Western blot analysis 14
Running 14
Transfer 14
Blocking 15
Detection 15
Alamar blue assay 15
Colony formation assay 16
Survival analysis 16
Results 18
Investigate miR-567 target genes in notorious cancer-related genes 18
The methodology of exploring miR-567 direct targets 19
miR-567 controls the biological effects in a fashion of directly inhibiting IGF1R, E2F1, and Cyclin B2 21
The clinical melanoma prognosis has a relationship with miR-567 and its interacting network 23
miR-567 prediction regulatory network involves in multiple cancer-related pathways 24
Conclusion and Discussion 27
miR-567 regulates multiple cancer driver genes, some of which are linked to melanoma prognosis or progression 27
miR-567 controls multiple pathways in cancer, having potential for cancer therapeutics 28
Future views 30
References 32
Appendix

參考文獻

1. Organization.(2018)., W.H., A report about cancer Retrieved from https://www.who.int/cancer/en/.
2. Chaffer, C.L. and R.A. Weinberg, A Perspective on Cancer Cell Metastasis. Science, 2011. 331(6024): p. 1559.
3. Houghton, A.N. and D. Polsky, Focus on melanoma. Cancer Cell, 2002. 2(4): p. 275-278.
4. Zbytek, B., et al., Current concepts of metastasis in melanoma. Expert Rev Dermatol, 2008. 3(5): p. 569-585.
5. Ribas, A., Adaptive Immune Resistance: How Cancer Protects from Immune Attack. Cancer Discovery, 2015. 5(9): p. 915-919.
6. Fecher, L.A., R.K. Amaravadi, and K.T. Flaherty, The MAPK pathway in melanoma. 2008. 20(2): p. 183-189.
7. Shakhova, O., et al., Sox10 promotes the formation and maintenance of giant congenital naevi and melanoma. Nat Cell Biol, 2012. 14(8): p. 882-90.
8. Forbes, S.A., et al., The Catalogue of Somatic Mutations in Cancer (COSMIC). Current protocols in human genetics, 2008. Chapter 10: p. Unit-10.11.
9. Hodis, E., A landscape of driver mutations in melanoma. Cell, 2012. 150: p. 251-263.
10. Dankort, D., BrafV600E cooperates with Pten loss to induce metastatic melanoma. Nat. Genet., 2009. 41: p. 544-552.
11. Tsao, H., et al., Genetic interaction between NRAS and BRAF mutations and PTEN/MMAC1 inactivation in melanoma. J. Invest. Dermatol., 2004. 122: p. 337-341.
12. Komiya, Y. and R. Habas, Wnt signal transduction pathways. Organogenesis, 2008. 4(2): p. 68-75.
13. Mosimann, C., G. Hausmann, and K. Basler, β-Catenin hits chromatin: regulation of Wnt target gene activation. Nature Reviews Molecular Cell Biology, 2009. 10: p. 276.
14. Kulikova, K., et al., Wnt Signaling Pathway and Its Significance for Melanoma Development. Vol. 2012. 2012. 107-111.
15. Javelaud, D., V.I. Alexaki, and A. Mauviel, Transforming growth factor-beta in cutaneous melanoma. Pigment Cell Melanoma Res, 2008. 21(2): p. 123-32.
16. Leivonen, S.-K. and V.-M. Kähäri, Transforming growth factor-β signaling in cancer invasion and metastasis. International Journal of Cancer, 2007. 121(10): p. 2119-2124.
17. Lee, R.C., The C. elegans Heterochronic Gene lin-4 Encodes Small RNAs
with Antisense Complementarity to lin-14. Cell, 1993. 75(843-854).
18. Wahid, F., et al., MicroRNAs: Synthesis, mechanism, function, and recent clinical trials. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2010. 1803(11): p. 1231-1243.
19. Meister, G., et al., Identification of novel argonaute-associated proteins. Curr Biol, 2005. 15(23): p. 2149-55.
20. Ingolia, N.T., et al., Genome-Wide Analysis in Vivo of Translation with Nucleotide Resolution Using Ribosome Profiling. Science, 2009. 324(5924): p. 218-223.
21. Tuschl, G.M.T., Mechanisms of gene silencing by
double-stranded RNA. Nature 2004.
22. Bartel, D.P., MicroRNAs: target recognition and regulatory functions. Cell, 2009. 136(2): p. 215-33.
23. Lee, I., et al., New class of microRNA targets containing simultaneous 5′-UTR and 3′-UTR interaction sites. Genome Research, 2009. 19(7): p. 1175-1183.
24. Forman, J.J. and H.A. Coller, The code within the code: microRNAs target coding regions. Cell cycle (Georgetown, Tex.), 2010. 9(8): p. 1533-1541.
25. MicroRNA Target Recognition: Insights from Transcriptome-Wide Non-Canonical Interactions. Molecules and Cells, 2016. 39(5): p. 375-381.
26. Calin, G.A., et al., Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A, 2004. 101(9): p. 2999-3004.
27. Esquela-Kerscher, A. and F.J. Slack, Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer, 2006. 6(4): p. 259-69.
28. Bader, A.G., D. Brown, and M. Winkler, The Promise of MicroRNA Replacement Therapy. Cancer Research, 2010. 70(18): p. 7027.
29. Li, X.J., Z.J. Ren, and J.H. Tang, MicroRNA-34a: a potential therapeutic target in human cancer. Cell Death &Amp; Disease, 2014. 5: p. e1327.
30. Rupaimoole, R. and F.J. Slack, MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov, 2017. 16(3): p. 203-222.
31. Gebert, L.F.R., et al., Miravirsen (SPC3649) can inhibit the biogenesis of miR-122. Nucleic Acids Research, 2014. 42(1): p. 609-621.
32. Betel, D., et al., The microRNA.org resource: targets and expression. Nucleic acids research, 2008. 36(Database issue): p. D149-D153.
33. Smalley, K.S., A pivotal role for ERK in the oncogenic behaviour of malignant melanoma? Int J Cancer, 2003. 104(5): p. 527-32.
34. Galaktionov, K. and D. Beach, Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: Evidence for multiple roles of mitotic cyclins. Cell, 1991. 67(6): p. 1181-1194.
35. Jackman, M., M. Firth, and J. Pines, Human cyclins B1 and B2 are localized to strikingly different structures: B1 to microtubules, B2 primarily to the Golgi apparatus. The EMBO journal, 1995. 14(8): p. 1646-1654.
36. Liu, J.H., et al., Functional association of TGF-β receptor II with cyclin B. Oncogene, 1999. 18: p. 269.
37. Alla, V., et al., E2F1 in Melanoma Progression and Metastasis. JNCI: Journal of the National Cancer Institute, 2010. 102(2): p. 127-133.
38. Rouaud, F., et al., E2F1 inhibition mediates cell death of metastatic melanoma. Cell Death Dis, 2018. 9(5): p. 527.
39. Mauerer, A., et al., Identification of new genes associated with melanoma. Experimental Dermatology, 2011. 20(6): p. 502-507.
40. Qin, J., H. Xin, and B.J. Nickoloff, Specifically targeting ERK1 or ERK2 kills melanoma cells. J Transl Med, 2012. 10: p. 15.
41. Kaufmann, W.K., et al., Defective cell cycle checkpoint functions in melanoma are associated with altered patterns of gene expression. J Invest Dermatol, 2008. 128(1): p. 175-87.
42. Villanueva, J., et al., Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K. Cancer cell, 2010. 18(6): p. 683-695.
43. Hallstrom, T.C., S. Mori, and J.R. Nevins, An E2F1-dependent gene expression program that determines the balance between proliferation and cell death. Cancer cell, 2008. 13(1): p. 11-22.
44. Li, C.-F., et al., E2F transcription factor 1 overexpression as a poor prognostic factor in patients with nasopharyngeal carcinomas. Biomarkers and Genomic Medicine, 2013. 5(1): p. 23-30.
45. Bertoli, G., et al., MicroRNA-567 dysregulation contributes to carcinogenesis of breast cancer, targeting tumor cell proliferation, and migration. Breast Cancer Research and Treatment, 2017. 161(3): p. 605-616.
46. Liu, D., et al., MicroRNA-567 inhibits cell proliferation, migration and invasion by targeting FGF5 in osteosarcoma. EXCLI journal, 2018. 17: p. 102-112.
47. Malumbres, M. and M. Barbacid, Mammalian cyclin-dependent kinases. Trends Biochem Sci, 2005. 30(11): p. 630-41.

指導教授

馬念涵(Nian-Han Ma)

審核日期

2019-1-21

推文