Matches in SemOpenAlex for { <https://semopenalex.org/work/W4386827367> ?p ?o ?g. }
Showing items 1 to 98 of
98
with 100 items per page.
- W4386827367 abstract "Abstract Xeroderma Pigmentosum C is a dermal hereditary disease. It is caused by a mutation in the DNA damage recognition protein XPC that belongs to the Nucleotide excision repair pathway. XPC patients exhibit a photosensitive phenotype and fail to repair UV induced DNA lesions leading to their accumulation and ultimate conversion to mutations and carcinomas. In an attempt to normalize this phenotype, we screened a library of siRNAs targeting the human kinases, given their role in different DNA repair pathways. WT and XPC immortalized patient fibroblasts were transfected with the library then irradiated with UVB to induce DNA damage. XPC phenotypic reversal was monitored by the quantification of decreased photosensitivity and increased DNA damage repair. Out of the 1292 kinase siRNAs tested, twenty-eight were selected cellular survival compared to cells transfected with non-targeting siRNA in XP-C irradiated cells. Out of the selected hits, two kinases, PIK3C3 and LATS1, induce more than 20% repair of 6-4PP DNA lesions. The down regulation of autophagy-related protein PIK3C3 alone had an exclusive photo protective effect on XP-C irradiated cells validated these effects also on primary XP-C patient fibroblasts and CRISPR-Cas9 generated XPC-KO keratinocytes. PIK3C3 knock down in XP-C cells ameliorated in UVB dose response analysis, decreased apoptosis and lowered phosphorylation of P53 with no effect on proliferation. More importantly, PIK3C3 knock down induced an increase in UVRAG expression, a previously reported cDNA conveying lower photosensitivity in XP-C cells. Attempts to improve the XPC photosensitive and deficient repair phenotype using PIK3C3 inhibitors could thus pave a way for new therapeutic approaches delaying or preventing tumor initiation." @default.
- W4386827367 created "2023-09-19" @default.
- W4386827367 creator A5022987465 @default.
- W4386827367 creator A5029103273 @default.
- W4386827367 creator A5062237886 @default.
- W4386827367 creator A5073376549 @default.
- W4386827367 creator A5073755556 @default.
- W4386827367 creator A5090218857 @default.
- W4386827367 date "2023-09-18" @default.
- W4386827367 modified "2023-09-26" @default.
- W4386827367 title "Synthetic rescue of XPC phenotype via PIK3C3 downregulation" @default.
- W4386827367 cites W1968585859 @default.
- W4386827367 cites W1982915980 @default.
- W4386827367 cites W2004257622 @default.
- W4386827367 cites W2028821370 @default.
- W4386827367 cites W2043654167 @default.
- W4386827367 cites W2055022346 @default.
- W4386827367 cites W2057224711 @default.
- W4386827367 cites W2060349031 @default.
- W4386827367 cites W2085719635 @default.
- W4386827367 cites W2114248978 @default.
- W4386827367 cites W2116914842 @default.
- W4386827367 cites W2153535991 @default.
- W4386827367 cites W2154414728 @default.
- W4386827367 cites W2388163742 @default.
- W4386827367 cites W2394915104 @default.
- W4386827367 cites W2891443059 @default.
- W4386827367 cites W2938891495 @default.
- W4386827367 cites W2966685999 @default.
- W4386827367 cites W3083492229 @default.
- W4386827367 cites W3107561618 @default.
- W4386827367 cites W4238567307 @default.
- W4386827367 doi "https://doi.org/10.21203/rs.3.rs-3293829/v1" @default.
- W4386827367 hasPublicationYear "2023" @default.
- W4386827367 type Work @default.
- W4386827367 citedByCount "0" @default.
- W4386827367 crossrefType "posted-content" @default.
- W4386827367 hasAuthorship W4386827367A5022987465 @default.
- W4386827367 hasAuthorship W4386827367A5029103273 @default.
- W4386827367 hasAuthorship W4386827367A5062237886 @default.
- W4386827367 hasAuthorship W4386827367A5073376549 @default.
- W4386827367 hasAuthorship W4386827367A5073755556 @default.
- W4386827367 hasAuthorship W4386827367A5090218857 @default.
- W4386827367 hasBestOaLocation W43868273671 @default.
- W4386827367 hasConcept C104317684 @default.
- W4386827367 hasConcept C104451858 @default.
- W4386827367 hasConcept C127561419 @default.
- W4386827367 hasConcept C127716648 @default.
- W4386827367 hasConcept C134935766 @default.
- W4386827367 hasConcept C143425029 @default.
- W4386827367 hasConcept C153911025 @default.
- W4386827367 hasConcept C184235292 @default.
- W4386827367 hasConcept C190283241 @default.
- W4386827367 hasConcept C22615655 @default.
- W4386827367 hasConcept C2778378917 @default.
- W4386827367 hasConcept C2778502085 @default.
- W4386827367 hasConcept C502942594 @default.
- W4386827367 hasConcept C54009773 @default.
- W4386827367 hasConcept C54355233 @default.
- W4386827367 hasConcept C552990157 @default.
- W4386827367 hasConcept C81885089 @default.
- W4386827367 hasConcept C86803240 @default.
- W4386827367 hasConcept C95444343 @default.
- W4386827367 hasConceptScore W4386827367C104317684 @default.
- W4386827367 hasConceptScore W4386827367C104451858 @default.
- W4386827367 hasConceptScore W4386827367C127561419 @default.
- W4386827367 hasConceptScore W4386827367C127716648 @default.
- W4386827367 hasConceptScore W4386827367C134935766 @default.
- W4386827367 hasConceptScore W4386827367C143425029 @default.
- W4386827367 hasConceptScore W4386827367C153911025 @default.
- W4386827367 hasConceptScore W4386827367C184235292 @default.
- W4386827367 hasConceptScore W4386827367C190283241 @default.
- W4386827367 hasConceptScore W4386827367C22615655 @default.
- W4386827367 hasConceptScore W4386827367C2778378917 @default.
- W4386827367 hasConceptScore W4386827367C2778502085 @default.
- W4386827367 hasConceptScore W4386827367C502942594 @default.
- W4386827367 hasConceptScore W4386827367C54009773 @default.
- W4386827367 hasConceptScore W4386827367C54355233 @default.
- W4386827367 hasConceptScore W4386827367C552990157 @default.
- W4386827367 hasConceptScore W4386827367C81885089 @default.
- W4386827367 hasConceptScore W4386827367C86803240 @default.
- W4386827367 hasConceptScore W4386827367C95444343 @default.
- W4386827367 hasLocation W43868273671 @default.
- W4386827367 hasOpenAccess W4386827367 @default.
- W4386827367 hasPrimaryLocation W43868273671 @default.
- W4386827367 hasRelatedWork W1972931407 @default.
- W4386827367 hasRelatedWork W1995991297 @default.
- W4386827367 hasRelatedWork W2102655424 @default.
- W4386827367 hasRelatedWork W2108192168 @default.
- W4386827367 hasRelatedWork W2123456626 @default.
- W4386827367 hasRelatedWork W2163508849 @default.
- W4386827367 hasRelatedWork W2599583505 @default.
- W4386827367 hasRelatedWork W80043557 @default.
- W4386827367 hasRelatedWork W809077599 @default.
- W4386827367 hasRelatedWork W919967506 @default.
- W4386827367 isParatext "false" @default.
- W4386827367 isRetracted "false" @default.
- W4386827367 workType "article" @default.