Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer with poor survival rates and a high risk of recurrence. The rarity of UPSC poses challenges to the discovery of novel targeted therapies. Therefore, the purpose of this dissertation was to identify novel therapeutic targets that could aid in the management of UPSC. To do so, we began with the relatively large cohort of UPSC cases in the TCGA data set, which was used to identify differentially expressed genes between UPSC and low-grade endometrioid endometrial carcinoma (EEC) and normal tissue.
We identified Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1) to be a gene of interest, as it was significantly upregulated in UPSC and correlated with poorer overall survival. These findings were validated through immunohistochemical analysis of an independent cohort of tumor samples. Due to its role as a deubiquitinating enzyme, we hypothesized that UCHL1 contributes to UPSC tumor progression by modulating the protein stability of target genes.
To test this hypothesis, we first examined the functional role of UCHL1 in UPSC progression. Subsequently, we found that UCHL1 silencing reduced cell proliferation in vitro and in vivo. The treatment of UPSC-bearing mice with the UCHL1-specific inhibitor LDN-57444 via intraperitoneal injection also reduced tumor growth and increased overall survival times.
Next, we found that the effect of UCHL1 on increased cell proliferation was due to its ability to stabilize cyclin B1 protein, an essential protein in mitotic progression. Specifically, we demonstrated that UCHL1 and cyclin B1 interact with each other in both the cytoplasm and nuclear space prior to mitosis. UCHL1 silencing increased the deubiquitination of cyclin B1, suggesting that UCHL1 counteracts the ubiquitination of cyclin B1 by the anaphase-promoting complex. Accordingly, UCHL1 silencing slowed the progression of cells into mitosis. Taken together, our findings indicate that UCHL1 impairs the degradation of cyclin B1, leading to uncontrolled cell cycle progression. In summary, we have identified UCHL1 as a prognostic marker for UPSC and a viable therapeutic target.
","abstract_html":"<p>Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer with poor survival rates and a high risk of recurrence. The rarity of UPSC poses challenges to the discovery of novel targeted therapies. Therefore, the purpose of this dissertation was to identify novel therapeutic targets that could aid in the management of UPSC. To do so, we began with the relatively large cohort of UPSC cases in the TCGA data set, which was used to identify differentially expressed genes between UPSC and low-grade endometrioid endometrial carcinoma (EEC) and normal tissue.</p> <p>We identified Ubiquitin Carboxyl-Terminal Hydrolase L1 (<em>UCHL1</em>) to be a gene of interest, as it was significantly upregulated in UPSC and correlated with poorer overall survival. These findings were validated through immunohistochemical analysis of an independent cohort of tumor samples. Due to its role as a deubiquitinating enzyme, we hypothesized that UCHL1 contributes to UPSC tumor progression by modulating the protein stability of target genes.</p> <p>To test this hypothesis, we first examined the functional role of UCHL1 in UPSC progression. Subsequently, we found that UCHL1 silencing reduced cell proliferation in vitro and in vivo. The treatment of UPSC-bearing mice with the UCHL1-specific inhibitor LDN-57444 via intraperitoneal injection also reduced tumor growth and increased overall survival times.</p> <p>Next, we found that the effect of UCHL1 on increased cell proliferation was due to its ability to stabilize cyclin B1 protein, an essential protein in mitotic progression. Specifically, we demonstrated that UCHL1 and cyclin B1 interact with each other in both the cytoplasm and nuclear space prior to mitosis. UCHL1 silencing increased the deubiquitination of cyclin B1, suggesting that UCHL1 counteracts the ubiquitination of cyclin B1 by the anaphase-promoting complex. Accordingly, UCHL1 silencing slowed the progression of cells into mitosis. Taken together, our findings indicate that UCHL1 impairs the degradation of cyclin B1, leading to uncontrolled cell cycle progression. In summary, we have identified UCHL1 as a prognostic marker for UPSC and a viable therapeutic target.</p>","abstract_has_math":false,"creators":["Kwan, Suet Ying","0000-0002-8222-3827
"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation (PhD)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Karen H Lu","Russell R Broaddus","Wenliang Li"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017-05-01T07:00:00Z","date_published":"2017-05-01T07:00:00Z","updated_at":"2026-07-24T05:50:16Z","subjects":["Endometrial cancer","uterine papillary serous carcinoma","UCHL1","cyclin B1","Cancer Biology","Medicine and Health Sciences","Oncology","Translational Medical Research"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/737","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Karen H Lu","Russell R Broaddus","Wenliang Li"]},{"key":"dc:creator","label":"Author","values":["Kwan, Suet Ying","0000-0002-8222-3827
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We identified Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1) to be a gene of interest, as it was significantly upregulated in UPSC and correlated with poorer overall survival. These findings were validated through immunohistochemical analysis of an independent cohort of tumor samples. Due to its role as a deubiquitinating enzyme, we hypothesized that UCHL1 contributes to UPSC tumor progression by modulating the protein stability of target genes.
To test this hypothesis, we first examined the functional role of UCHL1 in UPSC progression. Subsequently, we found that UCHL1 silencing reduced cell proliferation in vitro and in vivo. The treatment of UPSC-bearing mice with the UCHL1-specific inhibitor LDN-57444 via intraperitoneal injection also reduced tumor growth and increased overall survival times.
Next, we found that the effect of UCHL1 on increased cell proliferation was due to its ability to stabilize cyclin B1 protein, an essential protein in mitotic progression. Specifically, we demonstrated that UCHL1 and cyclin B1 interact with each other in both the cytoplasm and nuclear space prior to mitosis. UCHL1 silencing increased the deubiquitination of cyclin B1, suggesting that UCHL1 counteracts the ubiquitination of cyclin B1 by the anaphase-promoting complex. Accordingly, UCHL1 silencing slowed the progression of cells into mitosis. Taken together, our findings indicate that UCHL1 impairs the degradation of cyclin B1, leading to uncontrolled cell cycle progression. In summary, we have identified UCHL1 as a prognostic marker for UPSC and a viable therapeutic target.
"]},{"key":"dc:title","label":"Title","values":["Cyclin B1 Mediates The Effect of Uchl1 In Promoting Cell Cycle Progression In Uterine Papillary Serous Carcinoma"]}]}],"canonical_facts":{"dc:contributor":["Karen H Lu","Russell R Broaddus","Wenliang Li"],"dc:creator":["Kwan, Suet Ying","0000-0002-8222-3827
"],"dc:date.available":["2018-04-12T07:00:00Z"],"dc:description.abstract":["Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer with poor survival rates and a high risk of recurrence. The rarity of UPSC poses challenges to the discovery of novel targeted therapies. Therefore, the purpose of this dissertation was to identify novel therapeutic targets that could aid in the management of UPSC. To do so, we began with the relatively large cohort of UPSC cases in the TCGA data set, which was used to identify differentially expressed genes between UPSC and low-grade endometrioid endometrial carcinoma (EEC) and normal tissue.
We identified Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1) to be a gene of interest, as it was significantly upregulated in UPSC and correlated with poorer overall survival. These findings were validated through immunohistochemical analysis of an independent cohort of tumor samples. Due to its role as a deubiquitinating enzyme, we hypothesized that UCHL1 contributes to UPSC tumor progression by modulating the protein stability of target genes.
To test this hypothesis, we first examined the functional role of UCHL1 in UPSC progression. Subsequently, we found that UCHL1 silencing reduced cell proliferation in vitro and in vivo. The treatment of UPSC-bearing mice with the UCHL1-specific inhibitor LDN-57444 via intraperitoneal injection also reduced tumor growth and increased overall survival times.
Next, we found that the effect of UCHL1 on increased cell proliferation was due to its ability to stabilize cyclin B1 protein, an essential protein in mitotic progression. Specifically, we demonstrated that UCHL1 and cyclin B1 interact with each other in both the cytoplasm and nuclear space prior to mitosis. UCHL1 silencing increased the deubiquitination of cyclin B1, suggesting that UCHL1 counteracts the ubiquitination of cyclin B1 by the anaphase-promoting complex. Accordingly, UCHL1 silencing slowed the progression of cells into mitosis. Taken together, our findings indicate that UCHL1 impairs the degradation of cyclin B1, leading to uncontrolled cell cycle progression. In summary, we have identified UCHL1 as a prognostic marker for UPSC and a viable therapeutic target.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/737"],"dc:subject":["Endometrial cancer","uterine papillary serous carcinoma","UCHL1","cyclin B1","Cancer Biology","Medicine and Health Sciences","Oncology","Translational Medical Research"],"dc:title":["Cyclin B1 Mediates The Effect of Uchl1 In Promoting Cell Cycle Progression In Uterine Papillary Serous Carcinoma"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:50:16Z"}