探討miR-567在黑色素細胞瘤中的調控機制

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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)

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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

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指導教授

馬念涵(Nian-Han Ma)

審核日期

2019-1-21

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