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postgraduate thesis: Investigating the role of the forkhead box transcription factor FOXM1 against oxidative stress and DNA damage in human embryonic stem cells

TitleInvestigating the role of the forkhead box transcription factor FOXM1 against oxidative stress and DNA damage in human embryonic stem cells
Authors
Issue Date2015
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Leung, M. [梁文康]. (2015). Investigating the role of the forkhead box transcription factor FOXM1 against oxidative stress and DNA damage in human embryonic stem cells. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5388006
Abstract(MnSOD or SOD2) and catalase (CAT), which defend against reactive oxygen species. A number of DNA repair genes such asBRCA1 interacting protein C-terminal helicase 1 (BRIP1) and RAD51 recombinase (RAD51) have recently been shown to be the transcriptional targets of FOXM1. It is hypothesized that FOXM1 is a critical regulator for maintaining genome stability in hESCs. In this study, FOXM1 was found to be expressed at high levels in the hESC cell line VAL-3.Hydrogen peroxide, as a model oxidant and potent DNA damaging agent, was used to study the response of hESCs to oxidative stress and DNA damage. Cell viability and morphology of hESCs were assessed after exposure to hydrogen peroxide. Knockdown of FOXM1 using specific siRNAs reduced cell proliferation rate but did not affect pluripotency of VAL-3 hESCs. Moreover, loss of FOXM1 expression down-regulated the expression of antioxidant enzyme CAT and FOXM1-depleted VAL-3 cells became sensitized to oxidative stress. Interestingly, comparison of mRNA and protein levels suggested that the FOXM1 protein was stabilized under oxidative stress. Immunostaining of FOXM1 showed that oxidative stress could induce transient nuclear translocation of FOXM1 in hESCs. These findings suggested that FOXM1 may play important roles in protecting hESCs against oxidative stress and DNA damage by the stabilization and increased nuclear translocation of FOXM1 to control the expression of antioxidant enzymes. The underlying mechanisms on how FOXM1 is regulated in response to oxidative stress in hESCs require further investigation.
DegreeMaster of Philosophy
SubjectEmbryonic stem cells
Transcription factors
Oxidative stress
DNA damage
Dept/ProgramBiochemistry
Persistent Identifierhttp://hdl.handle.net/10722/222771

 

DC FieldValueLanguage
dc.contributor.authorLeung, Man-hong-
dc.contributor.author梁文康-
dc.date.accessioned2016-01-22T23:12:33Z-
dc.date.available2016-01-22T23:12:33Z-
dc.date.issued2015-
dc.identifier.citationLeung, M. [梁文康]. (2015). Investigating the role of the forkhead box transcription factor FOXM1 against oxidative stress and DNA damage in human embryonic stem cells. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5388006-
dc.identifier.urihttp://hdl.handle.net/10722/222771-
dc.description.abstract(MnSOD or SOD2) and catalase (CAT), which defend against reactive oxygen species. A number of DNA repair genes such asBRCA1 interacting protein C-terminal helicase 1 (BRIP1) and RAD51 recombinase (RAD51) have recently been shown to be the transcriptional targets of FOXM1. It is hypothesized that FOXM1 is a critical regulator for maintaining genome stability in hESCs. In this study, FOXM1 was found to be expressed at high levels in the hESC cell line VAL-3.Hydrogen peroxide, as a model oxidant and potent DNA damaging agent, was used to study the response of hESCs to oxidative stress and DNA damage. Cell viability and morphology of hESCs were assessed after exposure to hydrogen peroxide. Knockdown of FOXM1 using specific siRNAs reduced cell proliferation rate but did not affect pluripotency of VAL-3 hESCs. Moreover, loss of FOXM1 expression down-regulated the expression of antioxidant enzyme CAT and FOXM1-depleted VAL-3 cells became sensitized to oxidative stress. Interestingly, comparison of mRNA and protein levels suggested that the FOXM1 protein was stabilized under oxidative stress. Immunostaining of FOXM1 showed that oxidative stress could induce transient nuclear translocation of FOXM1 in hESCs. These findings suggested that FOXM1 may play important roles in protecting hESCs against oxidative stress and DNA damage by the stabilization and increased nuclear translocation of FOXM1 to control the expression of antioxidant enzymes. The underlying mechanisms on how FOXM1 is regulated in response to oxidative stress in hESCs require further investigation.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.lcshEmbryonic stem cells-
dc.subject.lcshTranscription factors-
dc.subject.lcshOxidative stress-
dc.subject.lcshDNA damage-
dc.titleInvestigating the role of the forkhead box transcription factor FOXM1 against oxidative stress and DNA damage in human embryonic stem cells-
dc.typePG_Thesis-
dc.identifier.hkulb5388006-
dc.description.thesisnameMaster of Philosophy-
dc.description.thesislevelMaster-
dc.description.thesisdisciplineBiochemistry-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b5388006-

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