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008 230915s2023 ncua obm 000 0 eng d;

035 a| (Sirsi) o1397376846;

035 a| (OCoLC)1397376846;

043 a| n-us---;

049 a| EREE;

100 1 a| Dorgham, Mohammed Gamal,e| author.?| UNAUTHORIZED;

245 10 a| m6A's unique and dynamic role in breast cancer progression /c| by Mohammed Gamal Dorgham.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2023.;

300 a| 1 online resource (110 pages) :b| illustrations (chiefly color).;

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text fileb| PDFc| 3.362 MB2| rda;

490 1 a| ECU Brody School of Medicine dissertation;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

502 b| Ph.D.c| East Carolina Universityd| 2023.;

502 a| Presented to the Faculty of the Department of Biochemistry and Molecular Biology;

500 a| Advisor: Kyle Mansfield;

500 a| Title from PDF t.p. (viewed November 13, 2024).;

520 3 a| Despite intense study, metastatic breast cancer is still the second leading cause of female death from cancer in the US. While many genetic lesions and environmental factors have been implicated in breast cancer progression, effective treatments are still lacking, suggesting that we are missing part of the puzzle. Epithelial to Mesenchymal Transition (EMT) is a genetic process by which breast cancer cells epithelial characteristics are changed into a more invasive and mobile mesenchymal phenotype through the downregulation of epithelial genes and pathways while simultaneously upregulating mesenchymal genes and pathways. In recent years, it has become clear that posttranscriptional regulation plays a key role in the aberrant gene expression underlying malignancy and metastasis. For example, the mRNA modification N6-methyladenosine (m6A) is involved in many post-transcriptional regulation processes including mRNA stability and translational efficiency and has been reported to be involved in many different cancer types, including breast cancer. Unfortunately, there are many characterizations of m6A's role in not just breast cancer, but all types of cancers that are often conflicting. For this study, we characterized the effects of decreasing mRNA m6A levels by knocking down METTL3 in the MCF10 genetically defined model of breast cancer. The goal of this study was to determine if effects on proliferation and migration differed based on the stage of disease progression. Here we report that knocking down METTL3 at distinct stages of breast cancer progression indeed shows unique effects at each stage. The early-stage breast cancer line showed a more proliferative phenotype with the knockdown of METTL3 while the transformed breast cancer line showed a more migratory phenotype. Interestingly, the metastasized breast cancer cell line showed almost no effect on phenotype with the knockdown of METTL3. Furthermore, our transcriptome wide analysis of these cell lines with the knockdown of METTL3 provided us with a possible mechanism of m6A regulating EMT thus resulting in these phenotypical changes we observed. Finally, this study may begin to address the controversy of m6A's role in cancer and suggests that m6A may have a dynamic role in cancer that depends on the stage of progression.;

504 a| Includes bibliographical references.;

650 2 a| Neoplasms.=| ^A917584;

650 2 a| 6-methyladenine.?| UNAUTHORIZED;

650 2 a| Neoplastic Processes.=| ^A932825;

650 2 a| Adenine.=| ^A1380399;

700 1 a| Mansfield, Kyle,e| degree supervisor.?| UNAUTHORIZED;

710 2 a| East Carolina University.b| Department of Biochemistry and Molecular Biology.?| UNAUTHORIZED;

830 0 a| ECU Brody School of Medicine dissertation.?| UNAUTHORIZED;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/13173;

949 o| wjh;

994 a| C0b| ERE;

096 a| WP 870;

596 a| 1 4;

998 a| 6234530;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 6234530-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 9/15/2023x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 6234530-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 9/15/2023x| ETDz| HERESOURCE;

m6A's unique and dynamic role in breast cancer progression / by Mohammed Gamal Dorgham.

Author/creator	Dorgham, Mohammed Gamal author.
Other author	Mansfield, Kyle, degree supervisor.
Other author	East Carolina University. Department of Biochemistry and Molecular Biology.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2023.
Description	1 online resource (110 pages) : illustrations (chiefly color).
Supplemental Content	Access via ScholarShip
Subjects	Neoplasms. 6-methyladenine. Neoplastic Processes. Adenine.

Series	ECU Brody School of Medicine dissertation ECU Brody School of Medicine dissertation. UNAUTHORIZED
Summary	Despite intense study, metastatic breast cancer is still the second leading cause of female death from cancer in the US. While many genetic lesions and environmental factors have been implicated in breast cancer progression, effective treatments are still lacking, suggesting that we are missing part of the puzzle. Epithelial to Mesenchymal Transition (EMT) is a genetic process by which breast cancer cells epithelial characteristics are changed into a more invasive and mobile mesenchymal phenotype through the downregulation of epithelial genes and pathways while simultaneously upregulating mesenchymal genes and pathways. In recent years, it has become clear that posttranscriptional regulation plays a key role in the aberrant gene expression underlying malignancy and metastasis. For example, the mRNA modification N6-methyladenosine (m6A) is involved in many post-transcriptional regulation processes including mRNA stability and translational efficiency and has been reported to be involved in many different cancer types, including breast cancer. Unfortunately, there are many characterizations of m6A's role in not just breast cancer, but all types of cancers that are often conflicting. For this study, we characterized the effects of decreasing mRNA m6A levels by knocking down METTL3 in the MCF10 genetically defined model of breast cancer. The goal of this study was to determine if effects on proliferation and migration differed based on the stage of disease progression. Here we report that knocking down METTL3 at distinct stages of breast cancer progression indeed shows unique effects at each stage. The early-stage breast cancer line showed a more proliferative phenotype with the knockdown of METTL3 while the transformed breast cancer line showed a more migratory phenotype. Interestingly, the metastasized breast cancer cell line showed almost no effect on phenotype with the knockdown of METTL3. Furthermore, our transcriptome wide analysis of these cell lines with the knockdown of METTL3 provided us with a possible mechanism of m6A regulating EMT thus resulting in these phenotypical changes we observed. Finally, this study may begin to address the controversy of m6A's role in cancer and suggests that m6A may have a dynamic role in cancer that depends on the stage of progression.
General note	Advisor: Kyle Mansfield
General note	Title from PDF t.p. (viewed November 13, 2024).
Dissertation note	Ph.D. East Carolina University 2023.
Dissertation note	Presented to the Faculty of the Department of Biochemistry and Molecular Biology
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

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m6A's unique and dynamic role in breast cancer progression / by Mohammed Gamal Dorgham.

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