Ionizing radiation regulates long non-coding RNAs in human peripheral blood mononuclear cells

Beer, Lucian; Nemec, Lucas; Wagner, Tanja; Ristl, Robin; Altenburger, Lukas M.; Ankersmit, Hendrik Jan; Mildner, Michael

doi:10.1093/jrr/rrw111

Cited by 27 publications

(27 citation statements)

References 37 publications

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“…Thus, gene expression changes in saliva have been assessed during radiation treatment for head and neck cancer [ 78 ]. Radiation-induced changes in non-coding RNAs such as miRNAs or recently discovered lncRNAs have also been investigated as potential radiation dosimetry biomarkers [ 79 – 84 ]. Since new “omics” approaches open the era of big data in biomarker discovery, large-scale proteomics studies have also been used to identify radiation biomarkers in blood [ 85 , 86 ], saliva [ 87 ] or even urine [ 88 – 90 ].…”

Section: Discussionmentioning

confidence: 99%

Candidate gene biodosimetry markers of exposure to external ionizing radiation in human blood: A systematic review

Lacombe

Sima²,

Amundson

et al. 2018

PLoS ONE

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PurposeTo compile a list of genes that have been reported to be affected by external ionizing radiation (IR) and to assess their performance as candidate biomarkers for individual human radiation dosimetry.MethodsEligible studies were identified through extensive searches of the online databases from 1978 to 2017. Original English-language publications of microarray studies assessing radiation-induced changes in gene expression levels in human blood after external IR were included. Genes identified in at least half of the selected studies were retained for bio-statistical analysis in order to evaluate their diagnostic ability.Results24 studies met the criteria and were included in this study. Radiation-induced expression of 10,170 unique genes was identified and the 31 genes that have been identified in at least 50% of studies (12/24 studies) were selected for diagnostic power analysis. Twenty-seven genes showed a significant Spearman’s correlation with radiation dose. Individually, TNFSF4, FDXR, MYC, ZMAT3 and GADD45A provided the best discrimination of radiation dose < 2 Gy and dose ≥ 2 Gy according to according to their maximized Youden’s index (0.67, 0.55, 0.55, 0.55 and 0.53 respectively). Moreover, 12 combinations of three genes display an area under the Receiver Operating Curve (ROC) curve (AUC) = 1 reinforcing the concept of biomarker combinations instead of looking for an ideal and unique biomarker.ConclusionGene expression is a promising approach for radiation dosimetry assessment. A list of robust candidate biomarkers has been identified from analysis of the studies published to date, confirming for example the potential of well-known genes such as FDXR and TNFSF4 or highlighting other promising gene such as ZMAT3. However, heterogeneity in protocols and analysis methods will require additional studies to confirm these results.

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Section: Discussionmentioning

confidence: 99%

Candidate gene biodosimetry markers of exposure to external ionizing radiation in human blood: A systematic review

Lacombe

Sima²,

Amundson

et al. 2018

PLoS ONE

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“…lncRNAs can be regulated by radiation as it showed radio-resistance in many kinds of cancer cells [26,27]. Researches have also discovered that lncRNAs transcripts were changed because of ultraviolet rays or ionizing radiation in peripheral blood mononuclear cell (PBMC) [28], thymocyte [29] and melanocyte [30]. LncRNA gas5 was discovered in various cancers to play a regulatory role in radiotherapy efficacy [31][32][33][34][35].…”

Section: Discussionmentioning

confidence: 99%

LncRNA gas5 regulates granulosa cell apoptosis and viability following radiation by x-ray via sponging miR-205- 5p and Wnt/β-catenin signaling pathway in granulosa cell tumor of ovary

Li¹,

Ma²,

Li³

et al. 2020

Trop. J. Pharm Res

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Purpose: To investigate the role of lncRNA gas5 in ovarian granulosa cells exposed to x-ray in granulosa cell tumor of ovary (GCTO). Methods: KGN cell line was exposed to X-ray to mimic the radiotherapy for GCSO patients in vitro, cell viability was checked by CCK8 assays. RNA expression of apoptosis-related genes was determined by quantitative reverse transcriptase-polymerase reaction (qRT-PCR) while Western Blot for biomarkers in wnt/β-catenin signaling. Differential expressions of lncRNA gas5 were examined after cells were exposed to a ray for 0,24,48hs. We over expressed gas5 and assessed resultant cell viability, apoptosis and signaling. The sponging between gas5 and miR-205-5p was verified by luciferase assay. CCK8, qRT-PCR and Western blot were applied to investigate the correlation between miR-205-5p, cell viability, and apoptosis after miR-205-5p augmentation. Similarly, interaction between gas5 and miR-205-5p was assessed after co-transfection of miR-205-5p mimics and oe-gas5. Finally, wnt inhibitor was used to study the role of signaling pathway in KGN cells. Results: Exposure of KGN to x-ray reduced cell viability and increased apoptosis. Gas5showed reduced expression in the cells, while miR-205-5p expression increased. Gas5 upregulation protected the cells against apoptosis and contributed to cell viability and activation of wnt//β-catenin signaling. lncRNA gas5 targeted miR-205-5p and miR-205-5p mimics counteracted the functions of up-regulated lncRNA gas5, regulating Wnt/β-catenin signaling pathway. Inactivation of Wnt/β-catenin suppressed cell viability. Conclusions: lncRNA gas5 regulates cell apoptosis and viability following cellular radiation, thus presenting a potential therapeutic target for the application radiotherapy in GCTO patients. Keywords: Ovary, Proliferation, Apoptosis, lncRNA gas5, Radiotherapy, β-catenin signaling

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“…Further, as reported, it can act as a sponge for many miRNAs, including miR-26a, and miR-145 [ 33 , 34 ]. Studies have demonstrated that TUG1 was expressed in PBMCs and T lymphocytes [ 15 , 16 ]. Software (LncBase Predicted v.2) predicted the binding between TUG1 and miR-214 .…”

Section: Discussionmentioning

confidence: 99%

“…TUG1 has been considered as an oncogene in many tumor cells [ 13 , 14 ]. Recent studies have demonstrated that TUG1 was expressed in peripheral blood mononuclear cells (PBMCs) and T lymphocytes [ 15 , 16 ]. However, the role of TUG1 in SCI has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Zhenbao Pill reduces Treg cell proportion in acute spinal cord injury rats by regulating TUG1/miR-214/HSP27 axis

Wujisiguleng

et al. 2018

Biosci. Rep.

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Background: Acute spinal cord injury (SCI) is one of the weakest pathologies that seriously affect the quality of life of patients. Objective: To study the mechanism of how Zhenbao Pill reduces Treg cell proportion and improves acute SCI. Methods: A rat SCI model was established. Flow cytometry analysis was performed to determine the Treg cell proportion. RNA immunoprecipitation (RIP) and RNA pull-down were applied in confirming taurine up-regulated gene 1 (TUG1) and miR-214 binding. Intrathecal injection of TUG1 siRNA was also conducted to determine the effect of TUG1 in vivo. Results: Zhenbao Pill promoted the expression of TUG1 and heat shock protein 27 (HSP27) protein, and reduced the expression of miR-214 and forkhead box protein p3 (Foxp3) as well as Treg cell proportion in a concentration-dependent manner in SCI rats or in vitro cultured CD4+ T cells. Knockdown of TUG1 reversed the high protein expression of HSP27 and the inhibition of Treg cell proportion as well as Foxp3 protein induced by Zhenbao Pill, and miR-214 inhibitor canceled the TUG1 knockdown effect. Further, miR-214 mimic reversed the inhibition of Treg cell proportion and Foxp3 protein expression by Zhenbao Pill, which was abolished by the overexpression of HSP27. The mechanism was validated in animal experiments. Conclusion: Zhenbao Pill regulated TUG1/miR-214/HSP27 signaling pathway to reduce Treg cell proportion and thus relieve acute SCI.

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Ionizing radiation regulates long non-coding RNAs in human peripheral blood mononuclear cells

Cited by 27 publications

References 37 publications

Candidate gene biodosimetry markers of exposure to external ionizing radiation in human blood: A systematic review

Candidate gene biodosimetry markers of exposure to external ionizing radiation in human blood: A systematic review

LncRNA gas5 regulates granulosa cell apoptosis and viability following radiation by x-ray via sponging miR-205- 5p and Wnt/β-catenin signaling pathway in granulosa cell tumor of ovary

Zhenbao Pill reduces Treg cell proportion in acute spinal cord injury rats by regulating TUG1/miR-214/HSP27 axis

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