Non-coding RNAs: An emerging player in DNA damage response

Zhang, Chunzhi; Peng, Guang

doi:10.1016/j.mrrev.2014.11.003

Cited by 92 publications

(62 citation statements)

References 123 publications

(137 reference statements)

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“…Long non-coding RNAs (lncRNAs) are mRNA-like transcripts that do not code for protein but are present in about 80% of transcriptions [124]. lncRNAs are divided into five classes: sense, antisense, bidirectional, intronic, and intergenic.…”

Section: Biomarkers For Radiation Injury and Efficacy Of Radiationmentioning

confidence: 99%

Nonhuman primates as models for the discovery and development of radiation countermeasures

Singh

Olabisi

2017

Expert Opinion on Drug Discovery

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Introduction Despite significant scientific advances over the past six decades toward the development of safe and effective radiation countermeasures for humans using animal models, only two pharmaceutical agents have been approved by United States Food and Drug Administration (US FDA) for hematopoietic acute radiation syndrome (H-ARS). Additional research efforts are needed to further develop large animal models for improving the prediction of clinical safety and effectiveness of radiation countermeasures for ARS and delayed effects of acute radiation exposure (DEARE) in humans. Area covered The authors review the suitability of animal models for the development of radiation countermeasures for ARS following the FDA Animal Rule with a special focus on nonhuman primate (NHP) models of ARS. There are seven centers in the United States currently conducting studies with irradiated NHPs, with the majority of studies being conducted with rhesus monkeys. Expert opinion The NHP model is considered the gold standard animal model for drug development and approval by the FDA. The lack of suitable substitutes to NHP models for predicting response in humans serves as a bottleneck for the development of radiation countermeasures. Additional large animal models need to be characterized to support the development and FDA-approval of new radiation countermeasures.

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Section: Biomarkers For Radiation Injury and Efficacy Of Radiationmentioning

confidence: 99%

Nonhuman primates as models for the discovery and development of radiation countermeasures

Singh

Olabisi

2017

Expert Opinion on Drug Discovery

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“…In almost all aspects of biology, lncRNAs have served as critical regulators2930. Accumulating evidences suggest that lncRNAs play functional roles in development of different cancers, including cancer initiation and progression30.…”

Section: Discussionmentioning

confidence: 99%

Theophylline controllable RNAi-based genetic switches regulate expression of lncRNA TINCR and malignant phenotypes in bladder cancer cells

Chen

Liu

et al. 2016

Sci Rep

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TINCR is a well-known lncRNA which acts as a master regulator in somatic differentiation development. However, it is still unclear whether TINCR is also involved in caner occurrence and progression. In this study, we observed that TINCR was up-regulated in bladder cancer tissues and cells and contributed to oncogenesis and cancer progression. Silencing TINCR expression inhibited cell proliferation and promoted apoptosis in vitro, indicating that TINCR may be the potential therapeutic target for treating bladder urothelial carcinoma. Thus we used the synthetic biology approach to create theophylline controllable RNAi-based genetic switches which silenced TINCR in a dosage-dependent manner. Both RNAi-OFF and ON switches can be used to quantitatively control the expression of TINCR in bladder cancer to suppress the progression of bladder cancer. These findings suggest that lncRNA-TINCR could promote bladder cancer development and progression and artificial control of its expression through inducible RNAi may represent a new kind of therapeutic strategy for treating human bladder cancer.

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“…The increase in HR efficiency associated with the ago1 mutant suggests that miRNAs may influence DSB repair. It was previously reported that miRNA transcription and maturation processes respond to DNA damage in human cell lines, and some miRNAs negatively regulate DSB repair core components 25, 26 . Similar mechanisms may also exist in plants to suppress DSB repair.…”

Section: Resultsmentioning

confidence: 99%

Efficient Generation of diRNAs Requires Components in the Posttranscriptional Gene Silencing Pathway

Miki

Zhu

Zhang

et al. 2017

Sci Rep

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It has been reported that double-stranded break (DSB)-induced small RNAs (diRNAs) are generated via the RNA-directed DNA methylation pathway and function in DSB repair in Arabidposis. However, important questions remain regarding the biogenesis and function of diRNAs. Here, we used CRISPR/Cas9- or TALEN-triggered DSBs to characterize diRNAs in Arabidopsis and rice. We found that 21-nt diRNAs were generated from a 35S promoter::GU-US reporter transgene targeted by CRISPR/Cas9. Unexpectedly, Pol II transcription of the transgene was required for efficient diRNA production and the level of diRNA accumulation correlated with the expression level of the transgene. diRNAs were not detected from CRISPR/Cas9- or TALEN-induced DSBs within the examined endogenous genes in Arabidopsis or rice. We also found that DCL4 and RDR6 that are known to be involved in posttranscriptional gene silencing were required to generate diRNAs. Our results suggest that DSBs are necessary but not sufficient for efficient diRNA generation and a high level of diRNAs is not necessary for DSB repair.

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Non-coding RNAs: An emerging player in DNA damage response

Cited by 92 publications

References 123 publications

Nonhuman primates as models for the discovery and development of radiation countermeasures

Nonhuman primates as models for the discovery and development of radiation countermeasures

Theophylline controllable RNAi-based genetic switches regulate expression of lncRNA TINCR and malignant phenotypes in bladder cancer cells

Efficient Generation of diRNAs Requires Components in the Posttranscriptional Gene Silencing Pathway

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