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• W2943025306 endingPage "100409" @default.
• W2943025306 startingPage "100409" @default.
• W2943025306 abstract "Abstract Genomic instability and genetic heterogeneity are typical hallmarks of cancer, including osteosarcoma (OS), a type of bone tumor. Inactivation of DNA repair pathways may play an important role in the initiation and progression of OS pathogenesis by increasing the mutation rate and genomic instability. However, there is still a lack of information on gene alterations and mutations that may increase the risk of osteosarcoma formation. Reprogramming OS cells to a primitive stage namely induced pluripotent stem cell (iPSC) state could be a useful disease model to understand the pathogenesis of OS and to bridge the current gap of knowledge on DNA repair mechanisms in reprogrammed OS cells. By using Yamanaka factors, OS cell lines, G-292 and Saos-2, were reprogrammed to iPSC lines, respectively iG-292 and iSaos-2, both of which demonstrated pluripotency similar to embryonic stem cells. However, only iG-292 was able to form teratoma. Subsequent microarray data showed significant down-regulation of DNA Damage Response (DDR) genes expression for both iG-292 and iSaos-2. A functional assay using UV-induced DNA damage approach demonstrated efficient DNA repair mechanism in iG-292. Further analysis of nucleotide excision repair (NER) genes demonstrated up-regulation of GADD45G, XPA, RPA, MNAT1, ERCC1, PCNA, and POLL, in iG-292. Up-regulation of GADD45G together with up-regulation of other NER genes synergistically repair UV damage by rapid removal of cyclobutane pyrimidine dimers. In conclusion, down-regulation of DDR genes in reprogrammed OS may render an enhanced state of genomic integrity in reprogrammed OS as compared to the parental cells. Thus, this study demonstrated for the first time DDR profile of reprogrammed OS cells and the probable involvement of GADD45G in the DNA repair mechanism of reprogrammed OS cells." @default.
• W2943025306 created "2019-05-09" @default.
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• W2943025306 date "2019-09-01" @default.
• W2943025306 modified "2023-09-27" @default.
• W2943025306 title "DNA repair efficiency associated with reprogrammed osteosarcoma cells" @default.
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• W2943025306 doi "https://doi.org/10.1016/j.genrep.2019.100409" @default.
• W2943025306 hasPublicationYear "2019" @default.
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