MicroRNAs, cancer and ionizing radiation: Where are we?

Marta, Gustavo Nader; Garicochea, Bernardo; Carvalho, André L.; Real, Juliana Monte; Kowalski, Luiz Paulo

doi:10.1590/1806-9282.61.03.275

Cited by 25 publications

(18 citation statements)

References 64 publications

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“…20 On the molecular level, radiation-induced damage initiates a complex signaling cascade in cells, resulting in a variety of responses that include cell cycle arrest, induction of stress-response genes, DNA repair, and apoptosis. 21 IR damage activates a number of stress-response-signaling pathways that contribute to lethality, and many of these may be independent of DNA damage. 20, 21 Radiation can also up or downregulate miRNA expression, and such alteration of miRNA expression profiles could affect the final outcome of radiation therapy.…”

Section: Discussionmentioning

confidence: 99%

“…21 IR damage activates a number of stress-response-signaling pathways that contribute to lethality, and many of these may be independent of DNA damage. 20, 21 Radiation can also up or downregulate miRNA expression, and such alteration of miRNA expression profiles could affect the final outcome of radiation therapy.…”

Section: Discussionmentioning

confidence: 99%

“…2, 9, 13 The IR-induced DDR modulates miRNA expression and biogenesis. In addition, Mao et al 23 and Marta et al 21 very recently reviewed IR-responsive miRNAs and their targets in various cell lines. Regulation of miRNAs was shown to influence cellular sensitivity to radiation, primarily through modulation of molecules involved in the DDR such as ATM, ATR, RAD51, and DNA-PK.…”

Section: Discussionmentioning

confidence: 99%

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Radiation-inducible miR-770-5p sensitizes tumors to radiation through direct targeting of PDZ-binding kinase

et al. 2017

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Radiotherapy represents the most effective non-surgical modality in cancer treatment. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression, and are involved in many biological processes and diseases. To identify miRNAs that influence the radiation response, we performed miRNA array analysis using MCF7 cells at 2, 8, and 24 h post irradiation. We demonstrated that miR-770-5p is a novel radiation-inducible miRNA. When miR-770-5p was overexpressed, relative cell number was reduced due to increased apoptosis in MCF7 and A549 cells. Transcriptomic and bioinformatic analyses revealed that PDZ-binding kinase (PBK) might be a possible target of miR-770-5p for regulation of radiosensitivity. PBK regulation mediated by direct targeting of miR-770-5p was demonstrated using luciferase reporter assays along with wild-type and mutant PBK-3′untranslated region constructs. Radiation sensitivity increased and decreased in miR-770-5p- and anti-miR-770-5p-transfected cells, respectively. Consistent with this result, transfection of short interfering RNA against PBK inhibited cell proliferation, while ectopic expression of PBK restored cell survival from miR-770-5p-induced cell death. In addition, miR-770-5p suppressed tumor growth, and miR-770-5p and PBK levels were inversely correlated in xenograft model mice. Altogether, these data demonstrated that miR-770-5p might be a useful therapeutic target miRNA that sensitizes tumors to radiation via negative regulation of PBK.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Radiation-inducible miR-770-5p sensitizes tumors to radiation through direct targeting of PDZ-binding kinase

et al. 2017

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“…(103, 104). Proton and gamma irradiation each result in unique changes in transcriptome regulation (105), gene methylation (106) and miRNA biogenesis (107, 108). Using protons and gamma sources, investigators at the Tufts University School of Medicine showed opposite angiogenic responses (L. Hlatky).…”

Section: Introductionmentioning

confidence: 99%

Understanding the Pathophysiology and Challenges of Development of Medical Countermeasures for Radiation-Induced Vascular/Endothelial Cell Injuries: Report of a NIAID Workshop, August 20, 2015

2016

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After the events of September 11, 2001, a decade of research on the development of medical countermeasures (MCMs) to treat victims of a radiological incident has yielded two FDA-approved agents to mitigate acute radiation syndrome. These licensed agents specifically target the mitigation of radiation-induced neutropenia and infection potential, while the ramifications of the exposure event in a public health emergency incident could include the entire body, causing additional acute and/or delayed organ/tissue injuries. Anecdotal data as well as recent findings from both radiation accident survivors and animal experiments implicate radiation-induced injury or dysfunction of the vascular endothelium leading to tissue and organ injuries. There are significant gaps in our understanding of the disease processes and progression, as well as the optimum approaches to develop medical countermeasures to mitigate radiation vascular injury. To address this issue, the Radiation and Nuclear Countermeasures Program of the National Institute of Allergy and Infectious Diseases (NIAID) organized a one-day workshop to examine the current state of the science in radiation-induced vascular injuries and organ dysfunction, the natural history of the pathophysiology and the product development maturity of potential medical countermeasures to treat these injuries. Meeting presentations were followed by a NIAID-led open discussion among academic investigators, industry researchers and government agency representatives. This article provides a summary of these presentations and subsequent discussion from the workshop.

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“…Further, miR-34a, which is upregulated after exposure to IR or etoposide, is another p53 target. miR-34a functions downstream of the p53 pathway as a tumor suppressor and is involved in regulating cell cycle arrest and apoptosis [106,107]. In addition to miR-34, it is well established that miR-21 targets many genes (Cdc25A, pAKt, PTEN) in the cell cycle arrest, DDR, and apoptotic pathways, and is consistently upregulated upon IR in a variety of normal and cancer cell lines [108,109].…”

Section: Mirna’s Therapeutic Function In Cancer Based On Its Regulmentioning

confidence: 99%

MicroRNAs, DNA Damage Response, and Cancer Treatment

Zhou

et al. 2016

IJMS

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As a result of various stresses, lesions caused by DNA-damaging agents occur constantly in each cell of the human body. Generally, DNA damage is recognized and repaired by the DNA damage response (DDR) machinery, and the cells survive. When repair fails, the genomic integrity of the cell is disrupted—a hallmark of cancer. In addition, the DDR plays a dual role in cancer development and therapy. Cancer radiotherapy and chemotherapy are designed to eliminate cancer cells by inducing DNA damage, which in turn can promote tumorigenesis. Over the past two decades, an increasing number of microRNAs (miRNAs), small noncoding RNAs, have been identified as participating in the processes regulating tumorigenesis and responses to cancer treatment with radiation therapy or genotoxic chemotherapies, by modulating the DDR. The purpose of this review is to summarize the recent findings on how miRNAs regulate the DDR and discuss the therapeutic functions of miRNAs in cancer in the context of DDR regulation.

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MicroRNAs, cancer and ionizing radiation: Where are we?

Cited by 25 publications

References 64 publications

Radiation-inducible miR-770-5p sensitizes tumors to radiation through direct targeting of PDZ-binding kinase

Radiation-inducible miR-770-5p sensitizes tumors to radiation through direct targeting of PDZ-binding kinase

Understanding the Pathophysiology and Challenges of Development of Medical Countermeasures for Radiation-Induced Vascular/Endothelial Cell Injuries: Report of a NIAID Workshop, August 20, 2015

MicroRNAs, DNA Damage Response, and Cancer Treatment

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