Radiation-induced alternative transcripts as detected in total and polysome-bound mRNA

Wahba, Amy; Ryan, Michaël; Shankavaram, Uma; Camphausen, Kevin; Tofilon, Philip J.

doi:10.18632/oncotarget.21672

Cited by 7 publications

(3 citation statements)

References 44 publications

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“…Ionizing radiation, among which X-rays, were shown to affect alternative splicing in various cell and tissue types including breast [53,54]. In our study, radiations were found to differentially influence the expression of VEGF alternative transcripts under iodide-deficient and -sufficient conditions.…”

Section: Discussionsupporting

confidence: 45%

Modulation of VEGF Expression and Oxidative Stress Response by Iodine Deficiency in Irradiated Cancerous and Non-Cancerous Breast Cells

Vanderstraeten

Baselet

Buset

et al. 2020

IJMS

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Breast cancer remains a major concern and its physiopathology is influenced by iodine deficiency (ID) and radiation exposure. Since radiation and ID can separately induce oxidative stress (OS) and microvascular responses in breast, their combination could additively increase these responses. Therefore, ID was induced in MCF7 and MCF12A breast cell lines by medium change. Cells were then X-irradiated with doses of 0.05, 0.1, or 3 Gy. In MCF12A cells, both ID and radiation (0.1 and 3 Gy) increased OS and vascular endothelial growth factor (VEGF) expression, with an additive effect when the highest dose was combined with ID. However, in MCF7 cells no additive effect was observed. VEGF mRNA up-regulation was reactive oxygen species (ROS)-dependent, involving radiation-induced mitochondrial ROS. Results on total VEGF mRNA hold true for the pro-angiogenic isoform VEGF165 mRNA, but the treatments did not modulate the anti-angiogenic isoform VEGF165b. Radiation-induced antioxidant response was differentially regulated upon ID in both cell lines. Thus, radiation response is modulated according to iodine status and cell type and can lead to additive effects on ROS and VEGF. As these are often involved in cancer initiation and progression, we believe that iodine status should be taken into account in radiation prevention policies.

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Section: Discussionsupporting

confidence: 45%

Modulation of VEGF Expression and Oxidative Stress Response by Iodine Deficiency in Irradiated Cancerous and Non-Cancerous Breast Cells

Vanderstraeten

Baselet

Buset

et al. 2020

IJMS

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“…Exposure to low-LET radiation not only changes gene expression but also triggers the production of alternative transcripts (due to alternative splicing or transcription) ( 47 , 53 – 55 ). A core signature of genes that become alternatively spliced in response to all radiation types was identified ( Figure 7A ).…”

Section: Resultsmentioning

confidence: 99%

High-LET Carbon and Iron Ions Elicit a Prolonged and Amplified p53 Signaling and Inflammatory Response Compared to low-LET X-Rays in Human Peripheral Blood Mononuclear Cells

et al. 2021

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Understanding the differences in biological response to photon and particle radiation is important for optimal exploitation of particle therapy for cancer patients, as well as for the adequate application of radiation protection measures for astronauts. To address this need, we compared the transcriptional profiles of isolated peripheral blood mononuclear cells 8 h after exposure to 1 Gy of X-rays, carbon ions or iron ions with those of non-irradiated cells using microarray technology. All genes that were found differentially expressed in response to either radiation type were up-regulated and predominantly controlled by p53. Quantitative PCR of selected genes revealed a significantly higher up-regulation 24 h after exposure to heavy ions as compared to X-rays, indicating their prolonged activation. This coincided with increased residual DNA damage as evidenced by quantitative γH2AX foci analysis. Furthermore, despite the converging p53 signature between radiation types, specific gene sets related to the immune response were significantly enriched in up-regulated genes following irradiation with heavy ions. In addition, irradiation, and in particular exposure to carbon ions, promoted transcript variation. Differences in basal and iron ion exposure-induced expression of DNA repair genes allowed the identification of a donor with distinct DNA repair profile. This suggests that gene signatures may serve as a sensitive indicator of individual DNA damage repair capacity. In conclusion, we have shown that photon and particle irradiation induce similar transcriptional pathways, albeit with variable amplitude and timing, but also elicit radiation type-specific responses that may have implications for cancer progression and treatment

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“…Cancer cells are vulnerable to splicing perturbations, leading to the exploitation of pharmacology and therapeutics. Recently, radiation has been proven to induce AS events, which may play a role in the radiation-induced translational control of gene expression and thus the cellular radioresponse [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

SRSF3 and HNRNPH1 Regulate Radiation-Induced Alternative Splicing of Protein Arginine Methyltransferase 5 in Hepatocellular Carcinoma

Wen

Tian

et al. 2022

IJMS

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Protein arginine methyltransferase 5 (PRMT5) is an epigenetic regulator which has been proven to be a potential target for cancer therapy. We observed that PRMT5 underwent alternative splicing (AS) and generated a spliced isoform PRMT5-ISO5 in hepatocellular carcinoma (HCC) patients after radiotherapy. However, the regulatory mechanism and the clinical implications of IR-induced PRMT5 AS are unclear. This work revealed that serine and arginine rich splicing factor 3 (SRSF3) silencing increased PRMT5-ISO5 level, whereas heterogeneous nuclear ribonucleoprotein H 1 (HNRNPH1) silencing reduced it. Then, we found that SRSF3 and HNRNPH1 competitively combined with PRMT5 pre-mRNA located at the region around the 3′- splicing site on intron 2 and the alternative 3′- splicing site on exon 4. IR-induced SRSF3 downregulation led to an elevated level of PRMT5-ISO5, and exogenous expression of PRMT5-ISO5 enhanced cell radiosensitivity. Finally, we confirmed in vivo that IR induced the increased level of PRMT5-ISO5 which in turn enhanced tumor killing and regression, and liver-specific Prmt5 depletion reduced hepatic steatosis and delayed tumor progression of spontaneous HCC. In conclusion, our data uncover the competitive antagonistic interaction of SRSF3 and HNRNPH1 in regulating PRMT5 splicing induced by IR, providing potentially effective radiotherapy by modulating PRMT5 splicing against HCC.

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Radiation-induced alternative transcripts as detected in total and polysome-bound mRNA

Cited by 7 publications

References 44 publications

Modulation of VEGF Expression and Oxidative Stress Response by Iodine Deficiency in Irradiated Cancerous and Non-Cancerous Breast Cells

Modulation of VEGF Expression and Oxidative Stress Response by Iodine Deficiency in Irradiated Cancerous and Non-Cancerous Breast Cells

High-LET Carbon and Iron Ions Elicit a Prolonged and Amplified p53 Signaling and Inflammatory Response Compared to low-LET X-Rays in Human Peripheral Blood Mononuclear Cells

SRSF3 and HNRNPH1 Regulate Radiation-Induced Alternative Splicing of Protein Arginine Methyltransferase 5 in Hepatocellular Carcinoma

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