MicroRNAs, DNA Damage Response, and Cancer Treatment

He, Mingyang; Zhou, Weiwei; Li, Chuang; Guo, Mingxiong

doi:10.3390/ijms17122087

Cited by 50 publications

(37 citation statements)

References 111 publications

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“…Thus, a dynamic and complex flux exists between RBP and miRNA regulation of mRNAs during disruption of homeostasis. As the role of miRNAs‐mediated regulation of mRNA stability during DDR has been extensively reported (reviewed in Han, Wan, Langley, Zhang, & Lu, ; He, Zhou, Li, & Guo, ; H. Hu & Gatti, ; Wan et al, ), here we will only discuss few examples of this regulatory mechanism. In the earlier steps of detection of DNA damage, miRNAs are involved in the regulation of key regulators of DDR, such as Ataxia‐telangiectasia‐mutated (ATM) (Maréchal & Zou, ).…”

Section: Deadenylation: Rbps and Micrornasmentioning

confidence: 99%

Connections between 3′ end processing and DNA damage response: Ten years later

Murphy

Kleiman

2019

WIREs RNA

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Ten years ago we reviewed how the cellular DNA damage response (DDR) is controlled by changes in the functional and structural properties of nuclear proteins, resulting in a timely coordinated control of gene expression that allows DNA repair. Expression of genes that play a role in DDR is regulated not only at transcriptional level during mRNA biosynthesis but also by changing steady‐state levels due to turnover of the transcripts. The 3′ end processing machinery, which is important in the regulation of mRNA stability, is involved in these gene‐specific responses to DNA damage. Here, we review the latest mechanistic connections described between 3′ end processing and DDR, with a special emphasis on alternative polyadenylation, microRNA and RNA binding proteins‐mediated deadenylation, and discuss the implications of deregulation of these steps in DDR and human disease. This article is categorized under: RNA Processing > 3′ End Processing RNA‐Based Catalysis > Miscellaneous RNA‐Catalyzed Reactions RNA in Disease and Development > RNA in Disease

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Section: Deadenylation: Rbps and Micrornasmentioning

confidence: 99%

Connections between 3′ end processing and DNA damage response: Ten years later

Murphy

Kleiman

2019

WIREs RNA

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“…This repair ability is closely related to the preferential activation of the DNA damage response (DDR), including repair of DNA and activation of the DNA damage checkpoint (7). Radiotherapy eliminates tumor cells by inducing DNA damage, while DDR sabotages radiotherapy (8). Inhibition of DDR enhances the radiosensitivity of tumor cells, and DDR-based therapies have been developed targeting molecules such as p21, WEE1, and NBS1 in osteosarcoma (9)(10)(11).…”

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confidence: 99%

CRIF1 as a potential target to improve the radiosensitivity of osteosarcoma

Ran

Jin

Xiang

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Resistance to ionizing radiation (IR), which is a conventional treatment for osteosarcoma that cannot be resected, undermines the efficacy of this therapy. However, the mechanism by which IR induces radioresistance in osteosarcoma is not defined. Here, we report that CR6-interacting factor-1 (CRIF1) is highly expressed in osteosarcoma and undergoes nuclear-cytoplasmic shuttling of cyclin-dependent kinase 2 (CDK2) after IR. Osteosarcoma cells lacking CRIF1 show increased sensitivity to IR, which is associated with delayed DNA damage repair, inactivated G1/S checkpoint, and mitochondrial dysfunction. CRIF1 interacts with the DNA damage checkpoint regulator CDK2, and CRIF1 and CDK2 colocalize in the nucleus after IR. Nuclear localization of CDK2 is associated with phosphorylation changes that promote DNA repair and activation of the G1/S checkpoint. CRIF1 knockdown synergized with IR in an in vivo osteosarcoma model, leading to tumor regression. Based on these findings, we identify CRIF1 as a potential therapeutic target in osteosarcoma that can increase the efficacy of radiotherapy. More broadly, our findings may provide insights into the mechanism for other types of radioresistant cancers and be exploited for therapeutic ends.

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“…The DDR is composed of a network of regulatory noncoding RNAs and proteins that act as sensors, transducers, and effectors [ 1 , 12 ]. Sensor proteins recognize specific lesions ( Figure 2 ).…”

Section: Dna Damage Responsementioning

confidence: 99%

DNA Damage as a Driver for Growth Delay: Chromosome Instability Syndromes with Intrauterine Growth Retardation

Teresa

Hernández-Gómez

Frı́as

2017

BioMed Research International

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DNA is constantly exposed to endogenous and exogenous mutagenic stimuli that are capable of producing diverse lesions. In order to protect the integrity of the genetic material, a wide array of DNA repair systems that can target each specific lesion has evolved. Despite the availability of several repair pathways, a common general program known as the DNA damage response (DDR) is stimulated to promote lesion detection, signaling, and repair in order to maintain genetic integrity. The genes that participate in these pathways are subject to mutation; a loss in their function would result in impaired DNA repair and genomic instability. When the DDR is constitutionally altered, every cell of the organism, starting from development, will show DNA damage and subsequent genomic instability. The cellular response to this is either uncontrolled proliferation and cell cycle deregulation that ensues overgrowth, or apoptosis and senescence that result in tissue hypoplasia. These diverging growth abnormalities can clinically translate as cancer or growth retardation; both features can be found in chromosome instability syndromes (CIS). The analysis of the clinical, cellular, and molecular phenotypes of CIS with intrauterine growth retardation allows inferring that replication alteration is their unifying feature.

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MicroRNAs, DNA Damage Response, and Cancer Treatment

Cited by 50 publications

References 111 publications

Connections between 3′ end processing and DNA damage response: Ten years later

Connections between 3′ end processing and DNA damage response: Ten years later

CRIF1 as a potential target to improve the radiosensitivity of osteosarcoma

DNA Damage as a Driver for Growth Delay: Chromosome Instability Syndromes with Intrauterine Growth Retardation

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