FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4224291693> ?p ?o ?g. }

• W4224291693 abstract "Abstract Background Osteosarcoma (OS) is a malignant bone tumor mostly occurring in children and adolescents, while chemotherapy resistance often develops and the mechanisms involved remain challenging to be fully investigated. Methods Genome-wide CRISPR screening combined with transcriptomic sequencing were used to identify the critical genes of doxorubicin resistance. Analysis of clinical samples and datasets, and in vitro and in vivo experiments (including CCK-8, apoptosis, western blot, qRT-PCR and mouse models) were applied to confirm the function of these genes. The bioinformatics and IP-MS assays were utilized to further verify the downstream pathway. RGD peptide-directed and exosome-delivered siRNA were developed for the novel therapy strategy. Results We identified that E3 ubiquitin-protein ligase Rad18 (Rad18) contributed to doxorubicin-resistance in OS. Further exploration revealed that Rad18 interact with meiotic recombination 11 (MRE11) to promote the formation of the MRE11-RAD50-NBS1 (MRN) complex, facilitating the activation of the homologous recombination (HR) pathway, which ultimately mediated DNA damage tolerance and leaded to a poor prognosis and chemotherapy response in patients with OS. Rad18-knockout effectively restored the chemotherapy response in vitro and in vivo. Also, RGD-exosome loading chemically modified siRad18 combined with doxorubicin, where exosome and chemical modification guaranteed the stability of siRad18 and the RGD peptide provided prominent targetability, had significantly improved antitumor activity of doxorubicin. Conclusions Collectively, our study identifies Rad18 as a driver of OS doxorubicin resistance that promotes the HR pathway and indicates that targeting Rad18 is an effective approach to overcome chemotherapy resistance in OS." @default.
• W4224291693 created "2022-04-26" @default.
• W4224291693 creator A5000328816 @default.
• W4224291693 creator A5014165481 @default.
• W4224291693 creator A5014305637 @default.
• W4224291693 creator A5019538077 @default.
• W4224291693 creator A5020497561 @default.
• W4224291693 creator A5024230638 @default.
• W4224291693 creator A5027503839 @default.
• W4224291693 creator A5030572879 @default.
• W4224291693 creator A5031783842 @default.
• W4224291693 creator A5034323855 @default.
• W4224291693 creator A5063171411 @default.
• W4224291693 creator A5064222660 @default.
• W4224291693 creator A5066825375 @default.
• W4224291693 creator A5072698553 @default.
• W4224291693 creator A5076699095 @default.
• W4224291693 date "2022-04-23" @default.
• W4224291693 modified "2023-10-14" @default.
• W4224291693 title "Genome-wide CRISPR screen identified Rad18 as a determinant of doxorubicin sensitivity in osteosarcoma" @default.
• W4224291693 cites W1971256943 @default.
• W4224291693 cites W1973260880 @default.
• W4224291693 cites W1984320346 @default.
• W4224291693 cites W1984919526 @default.
• W4224291693 cites W1994045445 @default.
• W4224291693 cites W1994954342 @default.
• W4224291693 cites W1996578865 @default.
• W4224291693 cites W1999644099 @default.
• W4224291693 cites W2006327227 @default.
• W4224291693 cites W2020920713 @default.
• W4224291693 cites W2027848959 @default.
• W4224291693 cites W2041699231 @default.
• W4224291693 cites W2047332524 @default.
• W4224291693 cites W2051193631 @default.
• W4224291693 cites W2061254282 @default.
• W4224291693 cites W2080978652 @default.
• W4224291693 cites W2081383642 @default.
• W4224291693 cites W2093984973 @default.
• W4224291693 cites W2097824787 @default.
• W4224291693 cites W2127749855 @default.
• W4224291693 cites W2140345256 @default.
• W4224291693 cites W2148098229 @default.
• W4224291693 cites W2152018334 @default.
• W4224291693 cites W2275099738 @default.
• W4224291693 cites W2473252551 @default.
• W4224291693 cites W2621898830 @default.
• W4224291693 cites W2743344940 @default.
• W4224291693 cites W2748645776 @default.
• W4224291693 cites W2794495801 @default.
• W4224291693 cites W2800392061 @default.
• W4224291693 cites W2898038371 @default.
• W4224291693 cites W2903480993 @default.
• W4224291693 cites W2914485568 @default.
• W4224291693 cites W2964017413 @default.
• W4224291693 cites W2964040556 @default.
• W4224291693 cites W2969354046 @default.
• W4224291693 cites W2980925374 @default.
• W4224291693 cites W2984780029 @default.
• W4224291693 cites W2990667881 @default.
• W4224291693 cites W2990895669 @default.
• W4224291693 cites W3009694030 @default.
• W4224291693 cites W3020234278 @default.
• W4224291693 cites W3029881948 @default.
• W4224291693 cites W3038325504 @default.
• W4224291693 cites W3080531908 @default.
• W4224291693 cites W3087198975 @default.
• W4224291693 cites W3089077900 @default.
• W4224291693 cites W3090626360 @default.
• W4224291693 cites W3138125859 @default.
• W4224291693 cites W3139433519 @default.
• W4224291693 cites W3174340986 @default.
• W4224291693 cites W3183763111 @default.
• W4224291693 cites W3186711657 @default.
• W4224291693 cites W3190653485 @default.
• W4224291693 cites W3192220958 @default.
• W4224291693 cites W3215794102 @default.
• W4224291693 doi "https://doi.org/10.1186/s13046-022-02344-y" @default.
• W4224291693 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35459258" @default.
• W4224291693 hasPublicationYear "2022" @default.
• W4224291693 type Work @default.
• W4224291693 citedByCount "6" @default.
• W4224291693 countsByYear W42242916932022 @default.
• W4224291693 countsByYear W42242916932023 @default.
• W4224291693 crossrefType "journal-article" @default.
• W4224291693 hasAuthorship W4224291693A5000328816 @default.
• W4224291693 hasAuthorship W4224291693A5014165481 @default.
• W4224291693 hasAuthorship W4224291693A5014305637 @default.
• W4224291693 hasAuthorship W4224291693A5019538077 @default.
• W4224291693 hasAuthorship W4224291693A5020497561 @default.
• W4224291693 hasAuthorship W4224291693A5024230638 @default.
• W4224291693 hasAuthorship W4224291693A5027503839 @default.
• W4224291693 hasAuthorship W4224291693A5030572879 @default.
• W4224291693 hasAuthorship W4224291693A5031783842 @default.
• W4224291693 hasAuthorship W4224291693A5034323855 @default.
• W4224291693 hasAuthorship W4224291693A5063171411 @default.
• W4224291693 hasAuthorship W4224291693A5064222660 @default.
• W4224291693 hasAuthorship W4224291693A5066825375 @default.
• W4224291693 hasAuthorship W4224291693A5072698553 @default.
• W4224291693 hasAuthorship W4224291693A5076699095 @default.
• W4224291693 hasBestOaLocation W42242916931 @default.

• next