Golgi Phosphoprotein 3 Mediates Radiation-Induced Bystander Effect via ERK/EGR1/TNF-α Signal Axis
The radiation-induced bystander effect (RIBE), an important non-targeted effect of radiation, has been proposed to be associated with irradiation-caused secondary cancers and reproductive damage beyond the irradiation-treated area after radiotherapy. However, the mechanisms for RIBE signal(s) regulation and transduction are not well understood. In the present work, we found that a Golgi protein, GOLPH3, was involved in RIBE transduction. Knocking down GOLPH3 in irradiated cells blocked the generation of the RIBE, whereas re-expression of GOLPH3 in knockdown cells rescued the RIBE. Furthermore, TNF-α was identified as an important intercellular signal molecule in the GOLPH3-mediated RIBE. A novel signal axis, GOLPH3/ERK/EGR1, was discovered to modulate the transcription of TNF-α and determine the level of released TNF-α. Our findings provide new insights into the molecular mechanism of the RIBE and a potential target for RIBE modulation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Antioxidants (Basel, Switzerland) - 11(2022), 11 vom: 01. Nov. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Qin, Feng [VerfasserIn] |
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| Links: |
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| Themen: |
EGR1 |
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| Anmerkungen: |
Date Revised 26.11.2022 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/antiox11112172 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a The radiation-induced bystander effect (RIBE), an important non-targeted effect of radiation, has been proposed to be associated with irradiation-caused secondary cancers and reproductive damage beyond the irradiation-treated area after radiotherapy. However, the mechanisms for RIBE signal(s) regulation and transduction are not well understood. In the present work, we found that a Golgi protein, GOLPH3, was involved in RIBE transduction. Knocking down GOLPH3 in irradiated cells blocked the generation of the RIBE, whereas re-expression of GOLPH3 in knockdown cells rescued the RIBE. Furthermore, TNF-α was identified as an important intercellular signal molecule in the GOLPH3-mediated RIBE. A novel signal axis, GOLPH3/ERK/EGR1, was discovered to modulate the transcription of TNF-α and determine the level of released TNF-α. Our findings provide new insights into the molecular mechanism of the RIBE and a potential target for RIBE modulation | ||
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| 700 | 1 | |a Chen, Guodong |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Kwan Ngok |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Miaomiao |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Kong, Peizhong |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Shengjie |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Mingyu |e verfasserin |4 aut | |
| 700 | 1 | |a Nie, Lili |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Wei |e verfasserin |4 aut | |
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