File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: The Valproate Mediates Radio-Bidirectional Regulation Through RFWD3-Dependent Ubiquitination on Rad51

TitleThe Valproate Mediates Radio-Bidirectional Regulation Through RFWD3-Dependent Ubiquitination on Rad51
Authors
Keywordsvalproate
radiosensitization
radioprotection
ubiquitination
RFWD3
Issue Date2021
PublisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/oncology
Citation
Frontiers in Oncology, 2021, v. 11, p. article no. 646256 How to Cite?
AbstractIonizing radiation (IR) can induce DNA double-strand breaks (DSBs) in tumor cells during radiotherapy (RT), but the efficiency of RT is limited because of the toxicity to normal cells. Locating an adjuvant treatment to alleviate damage in normal cells while sensitizing tumor cells to IR has attracted much attention. Here, using the 7,12-dimethylbenz[α]anthracene (DMBA)-induced malignant transformed MCF10A cells, we found that valproate (VPA), a histone deacetylase inhibitor (HDACi), radiosensitized transformed cells while alleviated IR-induced damage in normal cells at a safe dose (0.5 mM). We further demonstrated the decrease of homologous recombination (HR)-associated Rad51 in the transformed cells was related to the increase of its ubiquitination regulated by E3 ligase RFWD3 for the radiosensitization, which was opposite to normal cells, indicating that RFWD3-dependent ubiquitination on Rad51 was involved in the VPA-mediated radio-bidirectional effect. Through DMBA-transformed breast cancer rat model, VPA at 200 mg/kg radiosensitized tumor tissue cells by increasing RFWD3 and inhibited Rad51, while radioprotected normal tissue cells by decreasing RFWD3 and enhanced Rad51. In addition, we found high-level Rad51 was associated with tumorigenesis and poor prognosis in breast cancer patients. Our findings uncovered RFWD3-dependent Rad51 ubiquitination was the novel mechanism of VPA-mediated radio-bidirectional effect, VPA is a potential adjuvant treatment for tumor RT.
Persistent Identifierhttp://hdl.handle.net/10722/299293
ISSN
2023 Impact Factor: 3.5
2023 SCImago Journal Rankings: 1.066
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, G-
dc.contributor.authorLim, D-
dc.contributor.authorCai, Z-
dc.contributor.authorDing, W-
dc.contributor.authorTian, Z-
dc.contributor.authorDong, C-
dc.contributor.authorZhang, F-
dc.contributor.authorGuo, G-
dc.contributor.authorWang, X-
dc.contributor.authorZhou, P-
dc.contributor.authorFeng, Z-
dc.date.accessioned2021-05-10T06:59:45Z-
dc.date.available2021-05-10T06:59:45Z-
dc.date.issued2021-
dc.identifier.citationFrontiers in Oncology, 2021, v. 11, p. article no. 646256-
dc.identifier.issn2234-943X-
dc.identifier.urihttp://hdl.handle.net/10722/299293-
dc.description.abstractIonizing radiation (IR) can induce DNA double-strand breaks (DSBs) in tumor cells during radiotherapy (RT), but the efficiency of RT is limited because of the toxicity to normal cells. Locating an adjuvant treatment to alleviate damage in normal cells while sensitizing tumor cells to IR has attracted much attention. Here, using the 7,12-dimethylbenz[α]anthracene (DMBA)-induced malignant transformed MCF10A cells, we found that valproate (VPA), a histone deacetylase inhibitor (HDACi), radiosensitized transformed cells while alleviated IR-induced damage in normal cells at a safe dose (0.5 mM). We further demonstrated the decrease of homologous recombination (HR)-associated Rad51 in the transformed cells was related to the increase of its ubiquitination regulated by E3 ligase RFWD3 for the radiosensitization, which was opposite to normal cells, indicating that RFWD3-dependent ubiquitination on Rad51 was involved in the VPA-mediated radio-bidirectional effect. Through DMBA-transformed breast cancer rat model, VPA at 200 mg/kg radiosensitized tumor tissue cells by increasing RFWD3 and inhibited Rad51, while radioprotected normal tissue cells by decreasing RFWD3 and enhanced Rad51. In addition, we found high-level Rad51 was associated with tumorigenesis and poor prognosis in breast cancer patients. Our findings uncovered RFWD3-dependent Rad51 ubiquitination was the novel mechanism of VPA-mediated radio-bidirectional effect, VPA is a potential adjuvant treatment for tumor RT.-
dc.languageeng-
dc.publisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/oncology-
dc.relation.ispartofFrontiers in Oncology-
dc.rightsThis Document is Protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectvalproate-
dc.subjectradiosensitization-
dc.subjectradioprotection-
dc.subjectubiquitination-
dc.subjectRFWD3-
dc.titleThe Valproate Mediates Radio-Bidirectional Regulation Through RFWD3-Dependent Ubiquitination on Rad51-
dc.typeArticle-
dc.identifier.emailDong, C: dongchao@hku.hk-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3389/fonc.2021.646256-
dc.identifier.pmid33842359-
dc.identifier.pmcidPMC8029989-
dc.identifier.scopuseid_2-s2.0-85103881032-
dc.identifier.hkuros322419-
dc.identifier.volume11-
dc.identifier.spagearticle no. 646256-
dc.identifier.epagearticle no. 646256-
dc.identifier.isiWOS:000637885100001-
dc.publisher.placeSwitzerland-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats