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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/95014完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 俞松良 | zh_TW |
| dc.contributor.advisor | Sung-Liang Yu | en |
| dc.contributor.author | 姚芷玗 | zh_TW |
| dc.contributor.author | Chih-Yu Yao | en |
| dc.date.accessioned | 2024-08-26T16:15:28Z | - |
| dc.date.available | 2024-08-27 | - |
| dc.date.copyright | 2024-08-26 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-07-24 | - |
| dc.identifier.citation | Reference
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/95014 | - |
| dc.description.abstract | 肺癌是全球癌症死亡的主要原因。為了尋找有效的治療對策，研究著重於探討少數已知功能蛋白的分子機制，但肺癌的五年存活率仍舊沒有顯著的改善；反觀，未知功能的蛋白則可能暗藏著重要的分子機制，是過去一直被忽略的。在此，我們發現FAM241A，一個功能未知的蛋白質，在臺灣癌症登月計畫，研究肺腺癌的基因蛋白質體數據中，相較於正常肺組織，其表現量在腫瘤中呈現顯著下調。而臨床數據分析發現，FAM241A的表現與較好的預後和較低的病理侵襲性特徵有關。透過肺癌細胞實驗可以證實，FAM241A會抑制癌細胞的侵襲能力。後續的RNA定序分析中顯示，FAM241A過度表現之肺癌細胞中的差異表現基因顯著富集在細胞黏附和蛋白酶水解的路徑中，並可以上調細胞外基質（ECM）醣蛋白和分泌因子的基因轉錄。最後，利用免疫螢光染色和蛋白質相互作用分析，發現FAM241A主要表現於內質網中，並會參與在一個會增加細胞黏附性的ECM受體次單元─SGCD的轉譯後修飾，來增加SGCD的蛋白表現量。這項研究探討了FAM241A在肺腺癌中抑癌的功能，透過這些暗藏在未知功能蛋白中的機制，讓我們對肺腺癌的進展有更深的了解。 | zh_TW |
| dc.description.abstract | Lung cancer is the leading cause of cancer-related death worldwide. In the quest for biomarkers and effective treatment development, the uncharacterized proteins present a significant knowledge gap. We identified FAM241A, a protein with unknown function, as significantly downregulated in lung adenocarcinoma tumors in the Taiwan Cancer Moonshot cohort proteogenomic data. The clinical significance of FAM241A is validated using survival analysis using the TwCM cohort and the public databases. The clinicopathological analysis reveals that FAM241A is correlated with lower pathological invasive states. It is then validated in vitro that FAM241A expression inhibits lung cancer cell invasiveness. RNA-seq analysis indicates that FAM241A upregulates genes enriched in the cell adhesion and proteolysis pathways and genes of ECM glycoproteins and secreted factors. Finally, immunofluorescence staining and protein-protein interaction analysis reveal that FAM241A is localized in the ER and is implicated in the post-translational modification of an ECM receptor, SGCD, which enhances the adherence of epithelial cells to the basal lamina. This study explores the potential function of FAM241A as a tumor suppressor that enhances our understanding of the hidden mechanisms of uncharacterized proteins in lung adenocarcinoma. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-08-26T16:15:28Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-08-26T16:15:28Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員審定書 i
誌謝 ii 摘要 iii Abstract iv List of Figures vii List of Tables ix Chapter I Introduction 1 Non-small-cell lung cancer and Recurrence 1 The Dark Proteome and Human Proteome Project 2 Previous studies on FAM241 3 Chapter Ⅱ Specific Aim 6 Chapter Ⅲ Materials and Methods 7 Cell culture 7 RNA extraction, real-time quantitative PCR (qPCR), and RNA-sequencing 7 Protein extraction and Western blotting 8 Lentiviral transduction 8 Plasmid construction 9 Cell transfection 10 3-[4,5-Dimethylthiazole-2-yl]-2,5-diphenyltetrazolium Bromide (MTT) and Colony formation assays 10 Transwell migration and invasion assay 11 Immunofluorescent staining and confocal microscopy 11 Cycloheximide (CHX) chase experiment 12 Public databases 12 Statistical analysis 13 Chapter Ⅳ Results 14 FAM241A is downregulated in LUAD and correlates with a better prognosis 14 FAM241A is associated with a low invasive state in LUAD and may regulate cell adhesion through ECM interactions 15 FAM241A inhibits cell invasion in the NSCLC cell line without affecting cell migration, proliferation, and colony formation 16 FAM241A inhibits cancer cell invasion by regulating cell adhesion, proteolysis, and inflammation-related pathways. 17 FAM241A is an α-helix transmembrane protein partially localized in the endoplasmic reticulum. 19 FAM241A interacts with and enhances SGCD protein stability in CL1-5, presumably by promoting its post-translational modifications 22 Chapter Ⅴ Discussion 28 The uncharacterized proteins have clinical values 28 FAM241A reverses the invasive transformation in early-stage LUAD 28 FAM241A and ECM remodeling 30 FAM241A and post-translational modification 30 FAM241A specifically inhibits cancer cell invasion in LUAD 31 SGCD is a downstream effector of FAM241A 32 Conclusion and Future Perspectives 33 Figures 34 Tables 52 Supplementary Materials 54 Reference 72 | - |
| dc.language.iso | en | - |
| dc.subject | 抑癌 | zh_TW |
| dc.subject | 細胞外基質交互作用 | zh_TW |
| dc.subject | 肺腺癌 | zh_TW |
| dc.subject | FAM241A | zh_TW |
| dc.subject | 未知功能蛋白 | zh_TW |
| dc.subject | FAM241A | en |
| dc.subject | c4orf32 | en |
| dc.subject | LUAD | en |
| dc.subject | ECM interaction | en |
| dc.subject | Tumor suppressor | en |
| dc.subject | uPE1 | en |
| dc.title | FAM241A藉細胞外基質重塑來抑制肺腺癌細胞侵襲 | zh_TW |
| dc.title | FAM241A inhibits LUAD cancer cell invasiveness via ECM remodeling | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 潘思樺;陳玉如;蘇剛毅 | zh_TW |
| dc.contributor.oralexamcommittee | Szu-Hua Pan;Yu-Ju Chen;Su Kang-Yi | en |
| dc.subject.keyword | FAM241A,肺腺癌,細胞外基質交互作用,抑癌,未知功能蛋白, | zh_TW |
| dc.subject.keyword | FAM241A,c4orf32,LUAD,ECM interaction,Tumor suppressor,uPE1, | en |
| dc.relation.page | 76 | - |
| dc.identifier.doi | 10.6342/NTU202402217 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2024-07-26 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 醫學檢驗暨生物技術學系 | - |
| dc.date.embargo-lift | 2029-07-24 | - |
| 顯示於系所單位： | 醫學檢驗暨生物技術學系 | |
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