The Role of Circular RNAs in DNA Damage Response and Repair

Papaspyropoulos, Angelos; Hazapis, Orsalia; Lаgopati, Nefeli; Polyzou, Aikaterini; Papanastasiou, Anastasios D.; Liontos, Michalis; Gorgoulis, Vassilis G.; Kotsinas, Athanassios

doi:10.3390/cancers13215352

Cited by 10 publications

(4 citation statements)

References 107 publications

(188 reference statements)

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“…Because of the stable structures and attractive biological functions ( Huang et al, 2021 ; Papaspyropoulos et al, 2021 ), circRNAs are intrinsically resistant to degradation mediated by RNA exonuclease or RNase R and easily transferred into the body fluids by exosomes ( Burd et al, 2010 ). More important, exosome-carried circRNAs have been proved to be the candidate non-invasive biomarkers for the diagnosis and prognosis of cancer patients ( Wang et al, 2021c ; Li et al, 2021 ).…”

Section: Discussion and Perspectivementioning

confidence: 99%

Unraveling the significance of exosomal circRNAs in cancer therapeutic resistance

Kang

Yan²,

Liu³

et al. 2023

Front. Pharmacol.

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Exosomes are nanoscale extracellular vesicles secreted by a variety of cells, affecting the physiological and pathological homeostasis. They carry various cargoes including proteins, lipids, DNA, and RNA and have emerged as critical mediators of intercellular communication. During cell–cell communication, they can internalize either by autologous or heterologous recipient cells, which activate different signaling pathways, facilitating malignant progression of cancer. Among different types of cargoes in exosomes, the endogenous non-coding RNAs, such as circular RNAs (or circRNAs), have gained tremendous attention for their high stability and concentration, playing promising functional roles in cancer chemotherapeutic response by regulating the targeted gene expression. In this review, we primarily described the emerging evidence demonstrating the important roles of circular RNAs derived from exosomes in the regulation of cancer-associated signaling pathways that were involved in cancer research and therapeutic interventions. Additionally, the relevant profiles of exosomal circRNAs and their biological implications have been discussed, which is under investigation for their potential effect on the control of cancer therapeutic resistance.

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Section: Discussion and Perspectivementioning

confidence: 99%

Unraveling the significance of exosomal circRNAs in cancer therapeutic resistance

Kang

Yan²,

Liu³

et al. 2023

Front. Pharmacol.

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“…Interestingly, DNA damage has been shown to be accompanied by abnormal expression of non‐coding circRNAs. [ 24 , 25 , 26 ] Mechanistically, circRNAs act primarily by binding microRNAs after gene transcription. In addition, circRNA mechanisms may involve protein binding and regulation of protein function.…”

Section: Discussionmentioning

confidence: 99%

circCIMT Silencing Promotes Cadmium‐Induced Malignant Transformation of Lung Epithelial Cells Through the DNA Base Excision Repair Pathway

Chen

Cui

et al. 2023

Advanced Science

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Changes in gene expression in lung epithelial cells are detected in cancer tissues during exposure to pollutants, highlighting the importance of gene‐environmental interactions in disease. Here, a Cd‐induced malignant transformation model in mouse lungs and bronchial epithelial cell lines is constructed, and differences in the expression of non‐coding circRNAs are analyzed. The migratory and invasive abilities of Cd‐transformed cells are suppressed by circCIMT. A significant DNA damage response is observed after exposure to Cd, which increased further following circCIMT‐interference. It is found that APEX1 is significantly down‐regulated following Cd exposure. Furthermore, it is demonstrated that circCIMT bound to APEX1 during Cd exposure to mediate the DNA base excision repair (BER) pathway, thereby reducing DNA damage. In addition, simultaneous knockdown of both circCIMT and APEX1 promotes the expression of cancer‐related genes and malignant transformation after long‐term Cd exposure. Overall, these findings emphasis the importance of genetic‐epigenetic interactions in chemical‐induced cancer transformation.

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“…Nrf2 binds to the antioxidant-responsive elements (ARE) in the promoter regions of detoxification genes and also genes involved in the response to DNA damage, such as 8-oxoguanine glycosylase (OGG1) and p53 binding protein 1 (53BP1), triggering the transcription of these genes. Sestrins, a highly conserved family of small "antioxidant-like" proteins, which are activated by p53 under the influence of stressors and are involved in autophagy because they act as AMPK activators and maintain Nrf2 activation by this pathway, have also been proposed [62][63][64].…”

Section: P62/keap1/nrf2 System: the Relationship Between Autophagy An...mentioning

confidence: 99%

The Dual Role of Oxidative-Stress-Induced Autophagy in Cellular Senescence: Comprehension and Therapeutic Approaches

et al. 2023

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The contemporary lifestyle of the last decade has undeniably caused a tremendous increase in oxidative-stress-inducing environmental sources. This phenomenon is not only connected with the rise of ROS levels in multiple tissues but is also associated with the induction of senescence in different cell types. Several signaling pathways that are associated with the reduction in ROS levels and the regulation of the cell cycle are being activated, so that the organism can battle deleterious effects. Within this context, autophagy plays a significant role. Through autophagy, cells can maintain their homeostasis, as if it were a self-degradation process, which removes the “wounded” molecules from the cells and uses their materials as a substrate for the creation of new useful cell particles. However, the role of autophagy in senescence has both a “dark” and a “bright” side. This review is an attempt to reveal the mechanistic aspects of this dual role. Nanomedicine can play a significant role, providing materials that are able to act by either preventing ROS generation or controllably inducing it, thus functioning as potential therapeutic agents regulating the activation or inhibition of autophagy.

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The Role of Circular RNAs in DNA Damage Response and Repair

Cited by 10 publications

References 107 publications

Unraveling the significance of exosomal circRNAs in cancer therapeutic resistance

Unraveling the significance of exosomal circRNAs in cancer therapeutic resistance

circCIMT Silencing Promotes Cadmium‐Induced Malignant Transformation of Lung Epithelial Cells Through the DNA Base Excision Repair Pathway

The Dual Role of Oxidative-Stress-Induced Autophagy in Cellular Senescence: Comprehension and Therapeutic Approaches

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