The cross-talk between signaling pathways, noncoding RNAs and DNA damage response: Emerging players in cancer progression

Malakoti, Faezeh; Alemi, Forough; Younesi, Simin; Majidinia, Maryam; Yousefi, Bahman; Morovat, Pejman; Khelghati, Nafiseh; Maleki, Masoomeh; Karimian, Ansar; Asemi, Zatollah

doi:10.1016/j.dnarep.2020.103036

Cited by 14 publications

(9 citation statements)

References 110 publications

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“…P53 is the most important tumor suppressor of the cell, which normally has multiple functions, including inducing cell death or senescence, cell cycle arrest, and DNA repair. Upon stress response, p53 is activated and halts the cell cycle to removes the DNA damage by initiating the DDR pathway, which finally suppresses cancer progression (Green & Kroemer, 2009; Malakoti et al, 2021). However, mutations, which occur regularly in most cancer cells, disturb the core DNA binding domain of p53, and inactivate this protein.…”

Section: Pikk Family Members Are Activated In Response To Dna Damagementioning

confidence: 99%

Molecular mechanisms involved in DNA repair in human cancers: An overview of PI3k/Akt signaling and PIKKs crosstalk

Alemi

Sadigh

Malakoti

et al. 2021

Journal Cellular Physiology

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The cellular genome is frequently subjected to abundant endogenous and exogenous factors that induce DNA damage. Most of the Phosphatidylinositol 3-kinase-related kinases (PIKKs) family members are activated in response to DNA damage and are the most important DNA damage response (DDR) proteins. The DDR system protects the cells against the wrecking effects of these genotoxicants and repairs the DNA damage caused by them. If the DNA damage is severe, such as when DNA is the goal of chemo-radiotherapy, the DDR drives cells toward cell cycle arrest and apoptosis. Some intracellular pathways, such as PI3K/Akt, which is overactivated in most cancers, could stimulate the DDR process and failure of chemo-radiotherapy with the increasing repair of damaged DNA. This signaling pathway induces DNA repair through the regulation of proteins that are involved in DDR like BRCA1, HMGB1, and P53. In this review, we will focus on the crosstalk of the PI3K/Akt and PIKKs involved in DDR and then discuss current achievements in the sensitization of cancer cells to chemo-radiotherapy by PI3K/Akt inhibitors.

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Section: Pikk Family Members Are Activated In Response To Dna Damagementioning

confidence: 99%

Molecular mechanisms involved in DNA repair in human cancers: An overview of PI3k/Akt signaling and PIKKs crosstalk

Alemi

Sadigh

Malakoti

et al. 2021

Journal Cellular Physiology

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“…When the damages are limited, cell cycle arrest occurs and activates the DNA repair machinery to repair the damage sites and preserve genome stability. However, upon unrepairable damages due to Cis treatment, cancer cells are committed to apoptosis [18]. Mechanistically, following Cis therapy, DNA damage sensors and signal transducers including ATM and ATR recognize the damages and phosphorylate downstream factors including P53 and H2AX to determine cell fate, whether cell survival or apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Quercetin Augments Cisplatin-Induced Apoptosis, DNA Damage Response, and MiR-22 Expression While It Prevents DNA Repair in Osteosarcoma Cells

et al. 2022

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Background Osteosarcoma (OS) patients are commonly treated with chemotherapeutic agents like cisplatin (Cis). Quercetin with fewer side effects can improve the potency of chemotherapy and be used in combinational therapies. Herein, we aimed to evaluate the effects of Cis plus quercetin on DNA damage response (DDR), DNA repair, and apoptosis in Saos-2 cells. Methods The effects of Cis and quercetin single or in combination on Saos-2 cell viability and the cytotoxicity of the drugs were measured by MTT assay. The expression of DDR and repair components including P53, ATM, ATR, RAD51, and H2AX, and also miR-22 were analyzed by real-time PCR. The rate of apoptosis was measured by flow cytometry. Results Quercetin potentiated the cytotoxic effects of Cis in Saos-2 cells. The IC50 of Cis reduced from 6.12 µM to 4.25 µM. The combination of quercetin and Cis was associated with the up-regulation of miR-22 and DDR components, including P53, ATM, ATR, and H2AX as well as the down-regulation of RAD51. Moreover, this combined regimen significantly induced apoptosis in Saos-2 cells compared to mono drugs. Conclusion The co-treatment of quercetin and Cis can accelerate DNA damage, DNA damage response, and apoptosis while interfering with the DNA repair process in Saos-2 cells. Moreover, this combination provokes the tumor suppressor miR-22 expression in these cells.

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“…Therefore, defects in DNA repair genes reduce DDR functional activity and obtain cancerous behavior like escaping from apoptosis and subsequently increase malignancy’s predisposition like MMe. BAP1, XRCC1, PALB2, BRCA1, FANCI, ATM, SLX4, BRCA2, FANCC, FANCF, PMS1, and XPC are the most common mutated DNA repair genes in MMe [ 54 , 55 ] (Fig. 4 ).…”

Section: Dna Repair Machinery In Mesotheliomamentioning

confidence: 99%

“…Following a DSB, the MRN (MRE11, RAD50, NBS1) complex binds to the damage site, increases ATM activation, and activates a set of downstream proteins like BRCA1. Then, recombinase RAD51 is recruited by BRCA1 and mediates recombinase activity to complete the repair process [ 54 ]. In addition, the BRCA1/BARD1 complex regulates nucleosome and chromatin in the HR pathway [ 70 ].…”

Section: Dna Repair Machinery In Mesotheliomamentioning

confidence: 99%

“…BRCA1 associated protein 1 (BAP1) is a tumor suppressor protein involved in the regulation of fundamental cellular processes such as proliferation, differentiation, and apoptosis. Also, there is some encouraging evidence that BAP1 is a member of the BRCA1/BARD1 complex participating in the DDR pathway [ 54 ]. In addition, it has been reported that BAP1 contributes to other cellular mechanisms like cell cycle progression, genome stability, and DNA repair.…”

Section: Dna Repair Machinery In Mesotheliomamentioning

confidence: 99%

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DNA repair and damage pathways in mesothelioma development and therapy

et al. 2022

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Malignant mesothelioma (MMe) is an aggressive neoplasm that occurs through the transformation of mesothelial cells. Asbestos exposure is the main risk factor for MMe carcinogenesis. Other important etiologies for MMe development include DNA damage, over-activation of survival signaling pathways, and failure of DNA damage response (DDR). In this review article, first, we will describe the most important signaling pathways that contribute to MMe development and their interaction with DDR. Then, the contribution of DDR failure in MMe progression will be discussed. Finally, we will review the latest MMe therapeutic strategies that target the DDR pathway.

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The cross-talk between signaling pathways, noncoding RNAs and DNA damage response: Emerging players in cancer progression

Cited by 14 publications

References 110 publications

Molecular mechanisms involved in DNA repair in human cancers: An overview of PI3k/Akt signaling and PIKKs crosstalk

Molecular mechanisms involved in DNA repair in human cancers: An overview of PI3k/Akt signaling and PIKKs crosstalk

Quercetin Augments Cisplatin-Induced Apoptosis, DNA Damage Response, and MiR-22 Expression While It Prevents DNA Repair in Osteosarcoma Cells

DNA repair and damage pathways in mesothelioma development and therapy

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