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dc.contributor.authorShahzad, Naveed
dc.contributor.authorMunir, Tehreem
dc.contributor.authorJaved, Mariam
dc.contributor.authorTasneem, Fareeda
dc.contributor.authorAslam, Bilal
dc.contributor.authorAli, Moazzam
dc.contributor.authorMutahir, Zeeshan
dc.contributor.authorAkhtar Ali, Muhammad
dc.contributor.authorUmer, Muhammad
dc.contributor.authorAhmad, Munir
dc.contributor.authorFarooq, Kokab
dc.contributor.authorHassan, Umair
dc.contributor.authorMustafa, Tanveer
dc.contributor.authorAnjum, Rana Salman
dc.contributor.authorShakoori, Abdul Rauf
dc.date.accessioned2021-02-23T04:33:49Z
dc.date.available2021-02-23T04:33:49Z
dc.date.issued2020
dc.identifier.issn1932-6203
dc.identifier.doi10.1371/journal.pone.0236192
dc.identifier.urihttp://hdl.handle.net/10072/402518
dc.description.abstractBreast cancer (BC) is the foremost cause of cancer related deaths in women globally. Currently there is a scarcity of reliable biomarkers for its early stage diagnosis and theranostics monitoring. Altered DNA methylation patterns leading to the silencing of tumor suppressor genes are considered as an important mechanism underlying tumor development and progression in various cancer types, including BC. Very recently, epigenetic silencing of SHISA3, an antagonist of β-catenin, has been reported in various types of tumor. However, the role of SHISA3 in BC has not been investigated yet. Therefore, we aimed at evaluating the contribution of SHISA3 in BC causation by analyzing its expression and methylation levels in BC cell lines (MDA-MB231, MCF-7 and BT-474) and in 103 paired BC tissue samples. The SHISA3 expression and methylation status was determined by qPCR and methylation specific PCR (MSP) respectively. The role of SHISA3 in BC tumorigenesis was evaluated by proliferation and migration assays after ectopic expression of SHISA3. The association between SHISA3 hypermethylation and clinicopathological parameters of BC patients was also studied. The downregulation of SHISA3 expression was found in three BC cell lines used and in all BC tissue samples. However, SHISA3 promoter region was hypermethylated in 61% (63/103) tumorous tissues in comparison to the 18% of their matched normal tissues. The 5-aza-2’-deoxycytidine treatment restored SHISA3 expression by reversing promoter hypermethylation in both MDA-MB231 and MCF-7 cells. Furthermore, ectopic expression of SHISA3 significantly reduced the proliferation and migration ability of these cells. Taken together, our findings for the first time reveal epigenetic silencing and tumor suppressing role of SHISA3 in BC. Henceforth, this study has identified SHISA3 as potentially powerful target for the development of new therapies against BC, as well as novel diagnostic and therapy response monitoring approaches.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherPublic Library Science
dc.relation.ispartofpagefrome0236192
dc.relation.ispartofissue7
dc.relation.ispartofjournalPLoS One
dc.relation.ispartofvolume15
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchcode31
dc.subject.keywordsScience & Technology
dc.subject.keywordsMultidisciplinary Sciences
dc.subject.keywordsScience & Technology - Other Topics
dc.subject.keywordsDNA METHYLATION
dc.subject.keywordsWNT
dc.titleSHISA3, an antagonist of the Wnt/β-catenin signaling, is epigenetically silenced and its ectopic expression suppresses growth in breast cancer
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationShahzad, N; Munir, T; Javed, M; Tasneem, F; Aslam, B; Ali, M; Mutahir, Z; Akhtar Ali, M; Umer, M; Ahmad, M; Farooq, K; Hassan, U; Mustafa, T; Anjum, RS; Shakoori, AR, SHISA3, an antagonist of the Wnt/β-catenin signaling, is epigenetically silenced and its ectopic expression suppresses growth in breast cancer, PLoS One, 2020, 15 (7), pp. e0236192
dcterms.dateAccepted2020-06-30
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2021-02-23T04:31:22Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2020 Shahzad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
gro.hasfulltextFull Text
gro.griffith.authorUmer, Muhammad


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