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http://purl.uniprot.org/citations/37549780http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/37549780http://www.w3.org/2000/01/rdf-schema#comment"An active form of vitamin D3 (1,25-dihydroxyvitamin D3) acts through vitamin D receptor (VDR) initiating genomic response, but several studies described also non-genomic actions of 1,25-dihydroxyvitamin D3, implying the role of PDIA3 in the process. PDIA3 is a membrane-associated disulfide isomerase involved in disulfide bond formation, protein folding, and remodeling. Here, we used a transcriptome-based approach to identify changes in expression profiles in PDIA3-deficient squamous cell carcinoma line A431 after 1,25-dihydroxyvitamin D3 treatment. PDIA3 knockout led to changes in the expression of more than 2000 genes and modulated proliferation, cell cycle, and mobility of cells; suggesting an important regulatory role of PDIA3. PDIA3-deficient cells showed increased sensitivity to 1,25-dihydroxyvitamin D3, which led to decrease migration. 1,25-dihydroxyvitamin D3 treatment altered also genes expression profile of A431ΔPDIA3 in comparison to A431WT cells, indicating the existence of PDIA3-dependent genes. Interestingly, classic targets of VDR, including CAMP (Cathelicidin Antimicrobial Peptide), TRPV6 (Transient Receptor Potential Cation Channel Subfamily V Member 6), were regulated differently by 1,25-dihydroxyvitamin D3, in A431ΔPDIA3. Deletion of PDIA3 impaired 1,25-dihydroxyvitamin D3-response of genes, such as PTGS2, MMP12, and FOCAD, which were identified as PDIA3-dependent. Additionally, response to 1,25-dihydroxyvitamin D3 in cancerous A431 cells differed from immortalized HaCaT keratinocytes, used as non-cancerous control. Finally, silencing of PDIA3 and 1,25-dihydroxyvitamin D3, at least partially reverse the expression of cancer-related genes in A431 cells, thus targeting PDIA3 and use of 1,25-dihydroxyvitamin D3 could be considered in a prevention and therapy of the skin cancer. Taken together, PDIA3 has a strong impact on gene expression and physiology, including genomic response to 1,25-dihydroxyvitamin D3."xsd:string
http://purl.uniprot.org/citations/37549780http://purl.org/dc/terms/identifier"doi:10.1016/j.steroids.2023.109288"xsd:string
http://purl.uniprot.org/citations/37549780http://purl.uniprot.org/core/author"Olszewska A.M."xsd:string
http://purl.uniprot.org/citations/37549780http://purl.uniprot.org/core/author"Myszczynski K."xsd:string
http://purl.uniprot.org/citations/37549780http://purl.uniprot.org/core/author"Zmijewski M.A."xsd:string
http://purl.uniprot.org/citations/37549780http://purl.uniprot.org/core/author"Piotrowska A."xsd:string
http://purl.uniprot.org/citations/37549780http://purl.uniprot.org/core/author"Domzalski P."xsd:string
http://purl.uniprot.org/citations/37549780http://purl.uniprot.org/core/author"Nowak J.I."xsd:string
http://purl.uniprot.org/citations/37549780http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/37549780http://purl.uniprot.org/core/name"Steroids"xsd:string
http://purl.uniprot.org/citations/37549780http://purl.uniprot.org/core/pages"109288"xsd:string
http://purl.uniprot.org/citations/37549780http://purl.uniprot.org/core/title"PDIA3 modulates genomic response to 1,25-dihydroxyvitamin D3 in squamous cell carcinoma of the skin."xsd:string
http://purl.uniprot.org/citations/37549780http://purl.uniprot.org/core/volume"199"xsd:string
http://purl.uniprot.org/citations/37549780http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/37549780
http://purl.uniprot.org/citations/37549780http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/37549780
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http://purl.uniprot.org/uniprot/#_B3KQT2-mappedCitation-37549780http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/37549780
http://purl.uniprot.org/uniprot/#_B3KQT9-mappedCitation-37549780http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/37549780
http://purl.uniprot.org/uniprot/#_P30101-mappedCitation-37549780http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/37549780
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http://purl.uniprot.org/uniprot/P30101http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/37549780
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http://purl.uniprot.org/uniprot/V9HVY3http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/37549780