FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3215735318> ?p ?o ?g. }

• W3215735318 endingPage "1228" @default.
• W3215735318 startingPage "1216" @default.
• W3215735318 abstract "Purpose Radioresistance is a major cause of treatment failure in tumor radiation therapy, and the underlying mechanisms of radioresistance are still elusive. Golgi phosphoprotein 3 (GOLPH3) has been reported to associate tightly with cancer progression and chemoresistance. Herein, we explored whether GOLPH3 mediated radioresistance of lung adenocarcinoma (LUAD) and whether targeted suppression of GOLPH3 sensitized LUAD to radiation therapy. Methods and Materials The aberrant expression of GOLPH3 was evaluated by immunohistochemistry in LUAD clinical samples. To evaluate the association between GOLPH3 and radioresistance, colony formation and apoptosis were assessed in control and GOLPH3 knockdown cells. γ-H2AX foci and level determination and micronucleus test were used to analyze DNA damage production and repair. The rescue of GOLPH3 knockdown was then performed by exogenous expression of small interfering RNA-resistant mutant GOLPH3 to confirm the role of GOLPH3 in DNA damage repair. Mechanistically, the effect of GOLPH3 on regulating stability and nuclear accumulation of epidermal growth factor receptor (EGFR) and the activation of DNA-dependent protein kinase (DNA-PK) were investigated by quantitative real-time polymerase chain reaction, western blot, immunofluorescence, and coimmunoprecipitation. The role of GOLPH3 in vivo in radioresistance was determined in a xenograft model. Results In tumor tissues of 33 patients with LUAD, the expression of GOLPH3 showed significant increases compared with those in matched normal tissues. Knocking down GOLPH3 reduced the clonogenic capacity, impaired double-strand break (DSB) repair, and enhanced apoptosis after irradiation. In contrast, reversal of GOLPH3 depletion rescued the impaired repair of radiation-induced DSBs. Mechanistically, loss of GOLPH3 accelerated the degradation of EGFR in lysosome, causing the reduction in EGFR levels, thereby weakening nuclear accumulation of EGFR and attenuating the activation of DNA-PK. Furthermore, adenovirus-mediated GOLPH3 knockdown could enhance the ionizing radiation response in the LUAD xenograft model. Conclusions GOLPH3 conferred resistance of LUAD to ionizing radiation via stabilizing EGFR, and targeted suppression of GOLPH3 might be considered as a potential therapeutic strategy for sensitizing LUAD to radiation therapy. Radioresistance is a major cause of treatment failure in tumor radiation therapy, and the underlying mechanisms of radioresistance are still elusive. Golgi phosphoprotein 3 (GOLPH3) has been reported to associate tightly with cancer progression and chemoresistance. Herein, we explored whether GOLPH3 mediated radioresistance of lung adenocarcinoma (LUAD) and whether targeted suppression of GOLPH3 sensitized LUAD to radiation therapy. The aberrant expression of GOLPH3 was evaluated by immunohistochemistry in LUAD clinical samples. To evaluate the association between GOLPH3 and radioresistance, colony formation and apoptosis were assessed in control and GOLPH3 knockdown cells. γ-H2AX foci and level determination and micronucleus test were used to analyze DNA damage production and repair. The rescue of GOLPH3 knockdown was then performed by exogenous expression of small interfering RNA-resistant mutant GOLPH3 to confirm the role of GOLPH3 in DNA damage repair. Mechanistically, the effect of GOLPH3 on regulating stability and nuclear accumulation of epidermal growth factor receptor (EGFR) and the activation of DNA-dependent protein kinase (DNA-PK) were investigated by quantitative real-time polymerase chain reaction, western blot, immunofluorescence, and coimmunoprecipitation. The role of GOLPH3 in vivo in radioresistance was determined in a xenograft model. In tumor tissues of 33 patients with LUAD, the expression of GOLPH3 showed significant increases compared with those in matched normal tissues. Knocking down GOLPH3 reduced the clonogenic capacity, impaired double-strand break (DSB) repair, and enhanced apoptosis after irradiation. In contrast, reversal of GOLPH3 depletion rescued the impaired repair of radiation-induced DSBs. Mechanistically, loss of GOLPH3 accelerated the degradation of EGFR in lysosome, causing the reduction in EGFR levels, thereby weakening nuclear accumulation of EGFR and attenuating the activation of DNA-PK. Furthermore, adenovirus-mediated GOLPH3 knockdown could enhance the ionizing radiation response in the LUAD xenograft model. GOLPH3 conferred resistance of LUAD to ionizing radiation via stabilizing EGFR, and targeted suppression of GOLPH3 might be considered as a potential therapeutic strategy for sensitizing LUAD to radiation therapy." @default.
• W3215735318 created "2021-12-06" @default.
• W3215735318 creator A5005332302 @default.
• W3215735318 creator A5005544676 @default.
• W3215735318 creator A5005722282 @default.
• W3215735318 creator A5006157963 @default.
• W3215735318 creator A5016117514 @default.
• W3215735318 creator A5027432167 @default.
• W3215735318 creator A5027984633 @default.
• W3215735318 creator A5028227570 @default.
• W3215735318 creator A5028781688 @default.
• W3215735318 creator A5030596112 @default.
• W3215735318 creator A5038316000 @default.
• W3215735318 creator A5076875343 @default.
• W3215735318 date "2022-04-01" @default.
• W3215735318 modified "2023-09-28" @default.
• W3215735318 title "Golgi Phosphoprotein 3 Confers Radioresistance via Stabilizing EGFR in Lung Adenocarcinoma" @default.
• W3215735318 cites W1489503277 @default.
• W3215735318 cites W1586830290 @default.
• W3215735318 cites W1780348968 @default.
• W3215735318 cites W1968366677 @default.
• W3215735318 cites W1975509166 @default.
• W3215735318 cites W1983787599 @default.
• W3215735318 cites W1988106671 @default.
• W3215735318 cites W1994861590 @default.
• W3215735318 cites W1999365630 @default.
• W3215735318 cites W2030590316 @default.
• W3215735318 cites W2042108179 @default.
• W3215735318 cites W2043776284 @default.
• W3215735318 cites W2044151404 @default.
• W3215735318 cites W2048391838 @default.
• W3215735318 cites W2070151637 @default.
• W3215735318 cites W2072696652 @default.
• W3215735318 cites W2076971387 @default.
• W3215735318 cites W2091573051 @default.
• W3215735318 cites W2098217718 @default.
• W3215735318 cites W2105288740 @default.
• W3215735318 cites W2107277218 @default.
• W3215735318 cites W2109490882 @default.
• W3215735318 cites W2109826457 @default.
• W3215735318 cites W2112784018 @default.
• W3215735318 cites W2119915814 @default.
• W3215735318 cites W2123359660 @default.
• W3215735318 cites W2132834292 @default.
• W3215735318 cites W2135242557 @default.
• W3215735318 cites W2146331622 @default.
• W3215735318 cites W2152004734 @default.
• W3215735318 cites W2153243769 @default.
• W3215735318 cites W2155933329 @default.
• W3215735318 cites W2157079870 @default.
• W3215735318 cites W2164514441 @default.
• W3215735318 cites W2169663671 @default.
• W3215735318 cites W2514993735 @default.
• W3215735318 cites W2528730865 @default.
• W3215735318 cites W2620951738 @default.
• W3215735318 cites W2625452721 @default.
• W3215735318 cites W2765911149 @default.
• W3215735318 cites W2771018599 @default.
• W3215735318 cites W2806628670 @default.
• W3215735318 cites W3128646645 @default.
• W3215735318 doi "https://doi.org/10.1016/j.ijrobp.2021.11.023" @default.
• W3215735318 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34838866" @default.
• W3215735318 hasPublicationYear "2022" @default.
• W3215735318 type Work @default.
• W3215735318 sameAs 3215735318 @default.
• W3215735318 citedByCount "3" @default.
• W3215735318 countsByYear W32157353182022 @default.
• W3215735318 countsByYear W32157353182023 @default.
• W3215735318 crossrefType "journal-article" @default.
• W3215735318 hasAuthorship W3215735318A5005332302 @default.
• W3215735318 hasAuthorship W3215735318A5005544676 @default.
• W3215735318 hasAuthorship W3215735318A5005722282 @default.
• W3215735318 hasAuthorship W3215735318A5006157963 @default.
• W3215735318 hasAuthorship W3215735318A5016117514 @default.
• W3215735318 hasAuthorship W3215735318A5027432167 @default.
• W3215735318 hasAuthorship W3215735318A5027984633 @default.
• W3215735318 hasAuthorship W3215735318A5028227570 @default.
• W3215735318 hasAuthorship W3215735318A5028781688 @default.
• W3215735318 hasAuthorship W3215735318A5030596112 @default.
• W3215735318 hasAuthorship W3215735318A5038316000 @default.
• W3215735318 hasAuthorship W3215735318A5076875343 @default.
• W3215735318 hasBestOaLocation W32157353182 @default.
• W3215735318 hasConcept C117262875 @default.
• W3215735318 hasConcept C126322002 @default.
• W3215735318 hasConcept C134935766 @default.
• W3215735318 hasConcept C143425029 @default.
• W3215735318 hasConcept C173396325 @default.
• W3215735318 hasConcept C190283241 @default.
• W3215735318 hasConcept C502942594 @default.
• W3215735318 hasConcept C509974204 @default.
• W3215735318 hasConcept C54355233 @default.
• W3215735318 hasConcept C552990157 @default.
• W3215735318 hasConcept C55493867 @default.
• W3215735318 hasConcept C58962609 @default.
• W3215735318 hasConcept C71924100 @default.
• W3215735318 hasConcept C86803240 @default.
• W3215735318 hasConceptScore W3215735318C117262875 @default.
• W3215735318 hasConceptScore W3215735318C126322002 @default.

• next