In Vivo Delivery of miR-34a Sensitizes Lung Tumors to Radiation Through RAD51 Regulation

Cortez, María Angélica; Valdecanas, David R.; Niknam, Sharareh; Peltier, Heidi J.; Diao, Lixia; Giri, Uma; Komaki, Ritsuko; Calin, George A.; Gomez, Daniel R.; Chang, Joe Y.; Heymach, John V.; Bader, Andreas G.; Welsh, James W.

doi:10.1038/mtna.2015.47

Cited by 67 publications

(54 citation statements)

References 32 publications

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“…Recently, a study identified RAD51 as a new direct target of miR-34a able to increase radiosensitivity in NSCLC cells (Cortez et al, 2015). The authors found that miR-34a overexpression promoted both the downregulation of RAD51 and the reduction in radiation-induced RAD51 foci formation.…”

Section: Mir-34a and Tumor Radiosensitivitymentioning

confidence: 99%

Emergence of miR-34a in radiation therapy

Lacombe

Zenhausern

2017

Critical Reviews in Oncology/Hematology

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Expressions of many microRNAs (miRNAs) in response to ionizing radiation (IR) have already been investigated and some of them seem to play an important role in the tumor radioresistance, normal tissue radiotoxicity or as predictive biomarkers to radiation. MiR-34a is an emerging miRNA in recent radiobiology studies. Here, we review this miR-34 family member by detailing its different roles in radiation response and we will discuss about the role that it can play in radiation treatment. Thus, we will show that IR regulates miR-34a by increasing its expression. We will also highlight different biological processes involved in cellular response to IR and regulated by miR-34a in order to demonstrate the role it can play in tumor radio-response or normal tissue radiotoxicity as a radiosensitizer or radioprotector. MiR-34a is poised to assert itself as an important player in radiobiology and should become more and more important in radiation therapy management.

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Section: Mir-34a and Tumor Radiosensitivitymentioning

confidence: 99%

Emergence of miR-34a in radiation therapy

Lacombe

Zenhausern

2017

Critical Reviews in Oncology/Hematology

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“…miRNAs that interact with individual DDR components are shown in magenta. (1) miRNAs affect DDR sensors: miR-24 [18], miR-138 [20] and miR-542-3p [20] target H2AX; (2) miRNAs affect DDR mediators: miR-421 [22], miR-101 [23], miR-203 [24], miR-18a [25], miR-106a [25] and miR-27a [26] target ATM; and miR-185 [27] targets ATR; (3) miRNAs affect DNA repair by homologous recombination (HR): miR-9 [28], miR-24 [29], miR-182 [30] and let-7 [31] target BRCA1; let-7 [31] targets BRCA2; miR-145 [32] targets RAD6 and RAD18; miR-34a [33], miR-506 [34], miR-107 [35], miR-103 [35], miR-96 [36] and miR-155 [37] target RAD51; miR-92 [38] targets RAD21; miR-210 [39] and miR-373 [39] target RAD52; miR-205 [40] targets ZEB1 and UBC13; and miR-3940-5p [41] targets XRCC2; (4) miRNAs affect DNA repair by nonhomologous end joining (NHEJ): miR-101 [23] targets DNA-PK; and miR-890 [42] targets Ku80; (5) miRNAs affect cell cycle checkpoint: miR-15 [43], miR-497 [44] and let-7 [31] target CHK1; miR-630 [45], miR-504 [46], miR-125b [47] and miR-375 [48] target p53; miR-106b [49], miR-17 [38] and miR-92 [38] target p21; miR-124a [50], miR-885-5p [51], and miR-188-5p [52] target CDK2; miR-582-5p [53] targets CDK1; miR-200c [54] targets TBK1; miR-17 [55] and miR-20a [55] target FBXO31; miR-15 [43], miR-155 [43], miR-497 [44], and miR-890 [42] target WEE1; miR-16 [56], miR-21 [57], and miR-449a/b [58…”

Section: Figurementioning

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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“…It has been shown that miR-34a directly binds to the 3' untranslated region of RAD51 and regulates homologous recombination, preventing double-strand-break repair in NSCLC cells (Cortez et al, 2015). MiR-34a, a significant tumour-suppressing microRNA, and is downregulated in numerous types of cancer.…”

Section: Introductionmentioning

confidence: 99%

“…MiR-34a, a significant tumour-suppressing microRNA, and is downregulated in numerous types of cancer. Furthermore, Cortez et al (2015) demonstrated the therapeutic prospective of miR-34a transfer in combination with radiotherapy in mouse models of lung cancer. In conclusion, the authors recommended that administration of miR-34a in combination with radiotherapy may represent a new strategy for treating NSCLC (Cortez et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, Cortez et al (2015) demonstrated the therapeutic prospective of miR-34a transfer in combination with radiotherapy in mouse models of lung cancer. In conclusion, the authors recommended that administration of miR-34a in combination with radiotherapy may represent a new strategy for treating NSCLC (Cortez et al, 2015). Xiao et al (2015) aimed to inspect the miRNA expression outline in gastric stromal tumour tissues and to explore the role of dysregulated miRNAs by carrying out gene ontology (GO) and pathway improvement analysis; as a result of their research Xiao et al (2015) showed that there were 12 differently expressed microRNAs in gastric stromal tumour tissues, among which 10 miRNAs were down-controlled, and 2 were up-controlled (P<0.05).…”

Section: Introductionmentioning

confidence: 99%

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miRNA in Cancer Pathology

Alakeel¹,

Al-Doori

2017

JMBR

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MicroRNA/miRNA refers to types of RNA which are non-coding; they are21 to 25 nucleotides in length. In most cases, at particular nucleotide locations, they relate to one or more mRNAs. Deadenylation, cleavage, and alternative procedures of translation's suppression are the means by which miRNA disturb gene repression. Recent investigations seem to propose that miRNAs are involved in many cell procedures and for this they became perfect targets for usage in healing purposes. Various miRNAs are involved in the development of human vascular diseases, due to their function in modulating vascular cell proliferation, differentiation, migration and apoptosis via their targeted genes. Since vascular diseases are multifactorial and complex, numerous genes may be involved in their progression and regulation. Therefore, miRNAs can also have multiple gene targets, and in some instances, one gene can be modulated by various miRNAs. As of now, more than 800 human microRNAs have been identified using miBase, and work is still being conducted to search for and characterize new miRNAs. With rigorous clinical and fundamental studies, a clear understanding of how miRNAs function, in addition to the ways they can be used as biomarkers and targets for cancer and cardiovascular illnesses, will progress.

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In Vivo Delivery of miR-34a Sensitizes Lung Tumors to Radiation Through RAD51 Regulation

Cited by 67 publications

References 32 publications

Emergence of miR-34a in radiation therapy

Emergence of miR-34a in radiation therapy

MicroRNAs, DNA Damage Response, and Cancer Treatment

miRNA in Cancer Pathology

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