MiR-502 is the first reported miRNA simultaneously targeting two components of the classical non-homologous end joining (C-NHEJ) in pancreatic cell lines

Smolinska, Agnieszka; Swoboda, Julia; Fendler, Wojciech; Lerch, Markus M.; Sendler, Matthias; Moskwa, Patryk

doi:10.1016/j.heliyon.2020.e03187

Cited by 5 publications

(3 citation statements)

References 33 publications

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“…This latter suggests a role for miR-622 in regulating the balance between HR and NHEJ in the cell cycle [ 30 ]. It was demonstrated that miR-502 directly targets Ku70 and XLF in pancreatic cell lines, which might modulate both the assembly of the Ku70/80 complex and final steps of ligation during NHEJ; overexpression of this miRNA makes cells susceptible to DNA damage [ 31 ].…”

Section: Ku70/80mentioning

confidence: 99%

Interactions between miRNAs and Double-Strand Breaks DNA Repair Genes, Pursuing a Fine-Tuning of Repair

Peraza-Vega

Valverde

Rojas

2022

IJMS

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The repair of DNA damage is a crucial process for the correct maintenance of genetic information, thus, allowing the proper functioning of cells. Among the different types of lesions occurring in DNA, double-strand breaks (DSBs) are considered the most harmful type of lesion, which can result in significant loss of genetic information, leading to diseases, such as cancer. DSB repair occurs through two main mechanisms, called non-homologous end joining (NHEJ) and homologous recombination repair (HRR). There is evidence showing that miRNAs play an important role in the regulation of genes acting in NHEJ and HRR mechanisms, either through direct complementary binding to mRNA targets, thus, repressing translation, or by targeting other genes involved in the transcription and activity of DSB repair genes. Therefore, alteration of miRNA expression has an impact on the ability of cells to repair DSBs, which, in turn, affects cancer therapy sensitivity. This latter gives account of the importance of miRNAs as regulators of NHEJ and HRR and places them as a promising target to improve cancer therapy. Here, we review recent reports demonstrating an association between miRNAs and genes involved in NHEJ and HRR. We employed the Web of Science search query TS (“gene official symbol/gene aliases*” AND “miRNA/microRNA/miR-”) and focused on articles published in the last decade, between 2010 and 2021. We also performed a data analysis to represent miRNA–mRNA validated interactions from TarBase v.8, in order to offer an updated overview about the role of miRNAs as regulators of DSB repair.

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Section: Ku70/80mentioning

confidence: 99%

Interactions between miRNAs and Double-Strand Breaks DNA Repair Genes, Pursuing a Fine-Tuning of Repair

Peraza-Vega

Valverde

Rojas

2022

IJMS

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“…A recent paper showed that miR-502 overexpression increased the radiosensitivity of pancreatic cancer cell lines by targeting two proteins of the classical NHEJ repair pathway, Ku70 and XLF [ 122 ]. Mechanistically, miR-502 directly inhibits the DNA double-strand repair and also attenuates the cell cycle response upon radiation.…”

Section: Resultsmentioning

confidence: 99%

The Emerging Role of miRNAs for the Radiation Treatment of Pancreatic Cancer

Nguyen

Schilling

Dobiasch

et al. 2020

Cancers

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Today, pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide with a five-year overall survival rate of less than 7%. Only 15–20% of patients are eligible for curative intent surgery at the time of diagnosis. Therefore, neoadjuvant treatment regimens have been introduced in order to downsize the tumor by chemotherapy and radiotherapy. To further increase the efficacy of radiotherapy, novel molecular biomarkers are urgently needed to define the subgroup of pancreatic cancer patients who would benefit most from radiotherapy. MicroRNAs (miRNAs) could have the potential to serve as novel predictive and prognostic biomarkers in patients with pancreatic cancer. In the present article, the role of miRNAs as blood biomarkers, which are associated with either radioresistance or radiation-induced changes of miRNAs in pancreatic cancer, is discussed. Furthermore, the manuscript provides own data of miRNAs identified in a pancreatic cancer mouse model as well as radiation-induced miRNA changes in the plasma of tumor-bearing mice.

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“…In particular, there are many examples of RNAs controlling the expression of factors involved in the NHEJ mechanism, for instance, miR-101 and miR-874-3p target DNA-PKcs (as mentioned above). miR-124, miR-502 and miR-545 regulate Ku70 [144][145][146], miR-526b, miR-622 and miR-218-5p control the level of Ku80 [89,147,148], miR-34a suppresses the expression of 53BP1 [149]. For some factors, in addition to miRNA, competing endogenous RNAs (ceRNA) have been described that are able to counteract the effects of specific miRNAs by direct binding (Figure 5) [150]; for example, miR-4727-5p was shown to inhibit the expression of DNA ligase IV, while aforementioned ceRNA lnc-RI, reversed this effect [151].…”

Section: Different Types Of Rnas Are Involved In All Stages Of Nonhommentioning

confidence: 99%

The Role of RNA in DNA Breaks, Repair and Chromosomal Rearrangements

et al. 2021

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Incorrect reparation of DNA double-strand breaks (DSB) leading to chromosomal rearrangements is one of oncogenesis’s primary causes. Recently published data elucidate the key role of various types of RNA in DSB formation, recognition and repair. With growing interest in RNA biology, increasing RNAs are classified as crucial at the different stages of the main pathways of DSB repair in eukaryotic cells: nonhomologous end joining (NHEJ) and homology-directed repair (HDR). Gene mutations or variation in expression levels of such RNAs can lead to local DNA repair defects, increasing the chromosome aberration frequency. Moreover, it was demonstrated that some RNAs could stimulate long-range chromosomal rearrangements. In this review, we discuss recent evidence demonstrating the role of various RNAs in DSB formation and repair. We also consider how RNA may mediate certain chromosomal rearrangements in a sequence-specific manner.

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MiR-502 is the first reported miRNA simultaneously targeting two components of the classical non-homologous end joining (C-NHEJ) in pancreatic cell lines

Cited by 5 publications

References 33 publications

Interactions between miRNAs and Double-Strand Breaks DNA Repair Genes, Pursuing a Fine-Tuning of Repair

Interactions between miRNAs and Double-Strand Breaks DNA Repair Genes, Pursuing a Fine-Tuning of Repair

The Emerging Role of miRNAs for the Radiation Treatment of Pancreatic Cancer

The Role of RNA in DNA Breaks, Repair and Chromosomal Rearrangements

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