Grandt, Caine Lucas ; Brackmann, Lara Kim ; Poplawski, Alicia ; Schwarz, Heike ; Marini, Federico ; Hankeln, Thomas ; Galetzka, Danuta ; Zahnreich, Sebastian ; Mirsch, Johanna ; Spix, Claudia ; Blettner, Maria ; Schmidberger, Heinz ; Marron, Manuela (2023)
Identification of lncRNAs involved in response to ionizing radiation in fibroblasts of long-term survivors of childhood cancer and cancer-free controls.
In: Frontiers in Oncology, 2023, 13
doi: 10.26083/tuprints-00023854
Artikel, Zweitveröffentlichung, Verlagsversion
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Kurzbeschreibung (Abstract)
Introduction: Long non-coding ribonucleic acids (lncRNAs) are involved in the cellular damage response following exposure to ionizing radiation as applied in radiotherapy. However, the role of lncRNAs in radiation response concerning intrinsic susceptibility to late effects of radiation exposure has not been examined in general or in long-term survivors of childhood cancer with and without potentially radiotherapy-related second primary cancers, in particular.
Methods: Primary skin fibroblasts (n=52 each) of long-term childhood cancer survivors with a first primary cancer only (N1), at least one second primary neoplasm (N2+), as well as tumor-free controls (N0) from the KiKme case-control study were matched by sex, age, and additionally by year of diagnosis and entity of the first primary cancer. Fibroblasts were exposed to 0.05 and 2 Gray (Gy) X-rays. Differentially expressed lncRNAs were identified with and without interaction terms for donor group and dose. Weighted co-expression networks of lncRNA and mRNA were constructed using WGCNA. Resulting gene sets (modules) were correlated to the radiation doses and analyzed for biological function.
Results: After irradiation with 0.05Gy, few lncRNAs were differentially expressed (N0: AC004801.4; N1: PCCA-DT, AF129075.3, LINC00691, AL158206.1; N2+: LINC02315). In reaction to 2 Gy, the number of differentially expressed lncRNAs was higher (N0: 152, N1: 169, N2+: 146). After 2 Gy, AL109976.1 and AL158206.1 were prominently upregulated in all donor groups. The co-expression analysis identified two modules containing lncRNAs that were associated with 2 Gy (module1: 102 mRNAs and 4 lncRNAs: AL158206.1, AL109976.1, AC092171.5, TYMSOS, associated with p53-mediated reaction to DNA damage; module2: 390 mRNAs, 7 lncRNAs: AC004943.2, AC012073.1, AC026401.3, AC092718.4, MIR31HG, STXBP5-AS1, TMPO-AS1, associated with cell cycle regulation).
Discussion: For the first time, we identified the lncRNAs AL158206.1 and AL109976.1 as involved in the radiation response in primary fibroblasts by differential expression analysis. The co-expression analysis revealed a role of these lncRNAs in the DNA damage response and cell cycle regulation post-IR. These transcripts may be targets in cancer therapy against radiosensitivity, as well as provide grounds for the identification of at-risk patients for immediate adverse reactions in healthy tissues. With this work we deliver a broad basis and new leads for the examination of lncRNAs in the radiation response.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2023 |
| Autor(en): | Grandt, Caine Lucas ; Brackmann, Lara Kim ; Poplawski, Alicia ; Schwarz, Heike ; Marini, Federico ; Hankeln, Thomas ; Galetzka, Danuta ; Zahnreich, Sebastian ; Mirsch, Johanna ; Spix, Claudia ; Blettner, Maria ; Schmidberger, Heinz ; Marron, Manuela |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Identification of lncRNAs involved in response to ionizing radiation in fibroblasts of long-term survivors of childhood cancer and cancer-free controls |
| Sprache: | Englisch |
| Publikationsjahr: | 2023 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 2023 |
| Verlag: | Frontiers Media S.A. |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Frontiers in Oncology |
| Jahrgang/Volume einer Zeitschrift: | 13 |
| Kollation: | 18 Seiten |
| DOI: | 10.26083/tuprints-00023854 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/23854 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (Abstract): | Introduction: Long non-coding ribonucleic acids (lncRNAs) are involved in the cellular damage response following exposure to ionizing radiation as applied in radiotherapy. However, the role of lncRNAs in radiation response concerning intrinsic susceptibility to late effects of radiation exposure has not been examined in general or in long-term survivors of childhood cancer with and without potentially radiotherapy-related second primary cancers, in particular. Methods: Primary skin fibroblasts (n=52 each) of long-term childhood cancer survivors with a first primary cancer only (N1), at least one second primary neoplasm (N2+), as well as tumor-free controls (N0) from the KiKme case-control study were matched by sex, age, and additionally by year of diagnosis and entity of the first primary cancer. Fibroblasts were exposed to 0.05 and 2 Gray (Gy) X-rays. Differentially expressed lncRNAs were identified with and without interaction terms for donor group and dose. Weighted co-expression networks of lncRNA and mRNA were constructed using WGCNA. Resulting gene sets (modules) were correlated to the radiation doses and analyzed for biological function. Results: After irradiation with 0.05Gy, few lncRNAs were differentially expressed (N0: AC004801.4; N1: PCCA-DT, AF129075.3, LINC00691, AL158206.1; N2+: LINC02315). In reaction to 2 Gy, the number of differentially expressed lncRNAs was higher (N0: 152, N1: 169, N2+: 146). After 2 Gy, AL109976.1 and AL158206.1 were prominently upregulated in all donor groups. The co-expression analysis identified two modules containing lncRNAs that were associated with 2 Gy (module1: 102 mRNAs and 4 lncRNAs: AL158206.1, AL109976.1, AC092171.5, TYMSOS, associated with p53-mediated reaction to DNA damage; module2: 390 mRNAs, 7 lncRNAs: AC004943.2, AC012073.1, AC026401.3, AC092718.4, MIR31HG, STXBP5-AS1, TMPO-AS1, associated with cell cycle regulation). Discussion: For the first time, we identified the lncRNAs AL158206.1 and AL109976.1 as involved in the radiation response in primary fibroblasts by differential expression analysis. The co-expression analysis revealed a role of these lncRNAs in the DNA damage response and cell cycle regulation post-IR. These transcripts may be targets in cancer therapy against radiosensitivity, as well as provide grounds for the identification of at-risk patients for immediate adverse reactions in healthy tissues. With this work we deliver a broad basis and new leads for the examination of lncRNAs in the radiation response. |
| Freie Schlagworte: | weighted co-expression network analysis (WGCNA), differential gene expression analysis, RNA-Seq, radiation experiments, NGS - next generation sequencing, radiation response, KiKme Study |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-238547 |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin, Gesundheit |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Radiation Biology and DNA Repair |
| Hinterlegungsdatum: | 22 Aug 2023 13:56 |
| Letzte Änderung: | 23 Aug 2023 11:12 |
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| Suche nach Titel in: | TUfind oder in Google |
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- Identification of lncRNAs involved in response to ionizing radiation in fibroblasts of long-term survivors of childhood cancer and cancer-free controls. (deposited 22 Aug 2023 13:56) [Gegenwärtig angezeigt]
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