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ASPH inhibition reveals differential gene expression patterns in HPV-positive and HPV-negative cell lines

dc.contributor.authorKanwal, Madiha
dc.contributor.authorKasi, Murtaza Khan
dc.contributor.authorŠmahelová, Jana
dc.contributor.authorOlsen, Mark
dc.contributor.authorTachezy, Ruth
dc.contributor.authorŠmahel, Michal
dc.date.accessioned2024-10-14T09:45:52Z
dc.date.available2024-10-14T09:45:52Z
dc.date.issued2024
dc.identifier.urihttps://hdl.handle.net/20.500.14178/2663
dc.description.abstractCancer is associated with alterations in key cellular pathways, including the aspartate ββ-hydroxylase (ASPH) pathway, an oncogene upregulated in various carcinomas that plays a crucial role in tumor progression and metastasis. To elucidate the mechanisms of ASPH oncogenicity, we examined the effects of ASPH inhibition in human papillomavirus (HPV) HPV)-positive (CRL CRL-3240, HeLa) and HPV HPV-negative (FaDu, MCF MCF-7) cell lines. Inhibition of ASPH's catalytic activity using the small molecule inhibitor MO MO-II-1151 resulted in a significant reduction in proliferation, migration, and invasiveness of these tumor cells.Transcriptome analysis via bulk RNA sequencing revealed 2387 and 2350 differentially expressed genes in hypoxic and normoxic conditions, respectively, compared to controls.Notably, 1460 genes in hypoxia and 1325 in normoxia were significantly downregulated, particularly those involved in cell cycle regulation, DNA replication, and epithelial epithelial-mesenchymal transition (EMT). RT RT-qPCR validated the downregulation of key genes (IL7R, LY6D, LY6E, LY6K, TRIP13, SUV39H1, ELAVL2, WNT10B) in at least three cell lines. The interleukin 7 (IL7) receptor gene (IL7R) was consistently downregulated across all cell lines. IL7R, shared by the IL7 and thymic stromal lymphopoietin (TSLP) receptors, interacts with JAK1/3 and JAK1/2 through their intracellular domains. Western blot analysis showed that MOMO-II-1151 or tofacitinib (a Janus kinase inhibitor) reduced key JAK/STAT pathway components, including JAK2/3, STAT5, BCL BCL-2, MCL1, and cyclin D1 in CRL CRL-3240 and HeLa cells, indicating that ASPH inhibition primarily targets the JAK/STAT pathway via IL7. These findings suggest the potential of targeting IL7/TSLP receptor signaling and ASPH activity as therapeutic strategies in cancer treatment.en
dc.language.isoen
dc.publisherČeská společnost chemická
dc.rightsCreative Commons Uveďte původ 4.0 Internationalcs
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.titleASPH inhibition reveals differential gene expression patterns in HPV-positive and HPV-negative cell linesen
dcterms.accessRightsopenAccess
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/legalcode
dc.date.updated2024-10-14T09:45:52Z
dc.subject.keywordHPVen
dc.subject.keywordcanceren
dc.subject.keywordASPHen
dc.identifier.eissn2336-7210
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/MSM//LX22NPO5103
dc.date.embargoStartDate2024-10-14
dc.type.obd110
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.identifier.obd653786
dc.subject.rivPrimary30000::30200::30204
dc.subject.rivSecondary10000::10600::10607
dcterms.isPartOf.nameCzech Chemical Society Symposium Series
dcterms.isPartOf.issn2336-7202
dcterms.isPartOf.journalYear2024
dcterms.isPartOf.journalVolume22
dcterms.isPartOf.journalIssue6
uk.faculty.primaryId115
uk.faculty.primaryNamePřírodovědecká fakultacs
uk.faculty.primaryNameFaculty of Scienceen
uk.department.primaryId1034
uk.department.primaryNameKatedra genetiky a mikrobiologiecs
uk.department.primaryNameDepartment of Genetics and Microbiologyen
uk.event.nameThe third annual meeting of the National Institute of Virology and Bacteriology (NIVB)
dc.description.pageRange252-252
dc.type.obdHierarchyCsABSTRAKT::abstrakt::abstrakt v elektronické podoběcs
dc.type.obdHierarchyEnABSTRACT::abstract::abstract in e-formen
dc.type.obdHierarchyCode110::130::136en
uk.displayTitleASPH inhibition reveals differential gene expression patterns in HPV-positive and HPV-negative cell linesen


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