Investigating gene regulatory networks mediated by key transcription factors in the MCF-7 breast cancer cell line : MCF-7 유방암 세포주에서 주요 전사인자에 의해 매개되는 유전자 조절 네트워크 연구

다국어 초록 (Multilingual Abstract)

The gene regulatory mechanisms among key transcription factors in breast cancer are not well-studied. To elucidate these mechanisms, we employed a meta-analysis of ChIP-seq data from the MCF-7 cell line to characterize the binding levels of crucial transcription factors, investigate their functional relationships, and identify biomarkers for early diagnosis and personalized treatment strategies in breast cancer. Methods and Materials: ChIP-seq datasets for twelve transcription factors were obtained from the ENCODE project [21]. Peak identification was performed using HOMER with a stringent false discovery rate (FDR) adjustment [24]. The binding sites of transcription factors were analyzed to identify promoter, gene body, and intergenic regions. Binding site percentages were visualized using pie charts. Higher FPKM values indicated stronger binding regions, and the top 500 peaks were selected for further analysis [32]. Gene ontology (GO) analysis [26] was performed on these top binding sites, grouping transcription factors into functional categories such as cell cycle, estrogen signaling, transcriptional misregulation, and development. Results: Analysis revealed distinct binding patterns for each transcription factor. E2F1, E2F4, JUN, MYC, and SP1 primarily bind to promoter regions, whereas FOXA1, BRCA2, FOS, FOXM1, GATA3, HDAC2, and ESR1 predominantly bind to gene body and intergenic regions, suggesting different regulatory mechanisms. Unique binding site analysis identified JUN, FOXM1, and HDAC2 as potential therapeutic targets. Co-binding analysis identified 42 genes bound by at least six transcription factors, with 26 previously associated with breast cancer and 16 as potential new biomarkers. Discussion: The findings enhance the understanding of transcription factor dynamics in breast cancer by highlighting distinct regulatory roles. The identification of key regulatory regions and potential biomarkers offers new insights for therapeutic strategies. However, the study's reliance on a single cell line limits generalizability. Future research should validate these findings across various breast cancer subtypes and include experimental validations to confirm functional impacts. Overall, this study provides a detailed map of transcription factor activity in the MCF-7 cell line, contributing significantly to breast cancer biology and laying the groundwork for future research aimed at developing targeted therapies based on these findings.

목차 (Table of Contents)

• Abstract ⅰ
• Contents iii
• List of Figures · v
• List of Tables · vi
• Ⅰ. Introduction · 1
• 1.1 Breast Cancer 1
• 1.2 MCF-7 cell line 2
• 1.3 Roles of Key Transcription Factors in Breast Cancer 3
• 1.4 Research purpose 4
• Ⅱ. Materials and Methods 5
• 2.1 ChIP-seq Data Analysis 5
• 2.2 Gene Ontology Analysis · 5
• 2.3 Network Analysis · 6
• 2.4 Data Visualization 6
• Ⅲ. Results 7
• 3.1 Analysis of binding sites in MCF-7 Cell Line 7
• 3.2 Selection of Top 500 FPKM Binding Sites 10
• 3.3 Analysis Pipeline ·10
• 3.4 Pathway Grouping and Network Analysis 13
• 3.4.1 Cell Cycle 13
• 3.4.2 Estrogen Signaling 18
• 3.4.3 Transcriptional misregulation 22
• 3.4.4 Development ·26
• 3.5 Unique Binding Site Analysis 32
• 3.6 Co-binding Analysis and Biomarker Identification 36
• Ⅳ. Discussion 38
• V. References·40
• Supplements 47
• 국문초록 50