ROS as Regulators of Cellular Processes in Melanoma

Venza, Isabella; Visalli, Maria; Lentini, Germana; Teti, Diana; d’Alcontres, Francesco Stagno

doi:10.1155/2021/1208690

Cited by 26 publications

(21 citation statements)

References 207 publications

(221 reference statements)

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“…In addition to promoting genomic instability, UV-related ROS can affect nearly all cellular processes, contributing to the generation of the heavily oxidized milieu of melanoma [38][39][40][41][42]. On the other hand, the critical role of ROS not only in skin carcinogenesis, but also in other cancers, is widely recognized [73]. In particular, UV-derived ROS and their secondary mediators can modulate melanoma-related transduction pathways, modify cell metabolism and gene expression, and cause epigenetic changes.…”

Section: Discussionmentioning

confidence: 99%

“…As for other outdoor stressors, including ozone [15,72], UV radiation could regulate the expression of miRNAs via oxidative-stress-related processes [64,67,73]. Indeed, although via different mechanisms, both UV and atmospheric pollutants such as ozone, cigarette smoke, and particulate matter mainly disturb skin health by affecting the redox homeostasis of the tissue via ROS production [17,34,44,46,49,74].…”

Section: Uv-induced Redox Imbalance Modulates Redox-sensitive Mirnasmentioning

confidence: 99%

“…Based on the above evidence, in addition to specific genomic alterations, epigenetic modifications such as those linked to UV-induced deregulation of redox-sensitive miRNAs represent a further mechanism involved in cancer initiation and progression by affecting target genes linked to signaling pathways associated with melanomagenesis [66,73]. In this section, we will summarize some evidence demonstrating a role of UV-mediated redox mechanisms in the dysregulation of miRNAs involved in melanoma development and progression (Table 2).…”

Section: Uv-dysregulated Redox-sensitive Mirnas Involved In Melanoma ...mentioning

confidence: 99%

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Oxidative-Stress-Sensitive microRNAs in UV-Promoted Development of Melanoma

Pecorelli

Valacchi

2022

Cancers

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Melanoma is the most aggressive and life-threatening form of skin cancer. Key molecular events underlying the melanocytic transformation into malignant melanoma mainly involve gene mutations in which exposure to ultraviolet (UV) radiation plays a prominent role. However, several aspects of UV-induced melanomagenesis remain to be explored. Interestingly, redox-mediated signaling and perturbed microRNA (miRNA) profiles appear to be interconnected contributing factors able to act synergistically in melanoma initiation and progression. Since UV radiation can promote both redox imbalance and miRNA dysregulation, a harmful crosstalk between these two key cellular networks, with UV as central hub among them, is likely to occur in skin tissue. Therefore, decoding the complex circuits that orchestrate the interaction of UV exposure, oxidative stress, and dysregulated miRNA profiling can provide a deep understanding of the molecular basis of the melanomagenesis process. Furthermore, these mechanistic insights into the reciprocal regulation between these systems could have relevant implications for future therapeutic approaches aimed at counteracting UV-induced redox and miRNome imbalances for the prevention and treatment of malignant melanoma. In this review, we illustrate current information on the intricate connection between UV-induced dysregulation of redox-sensitive miRNAs and well-known signaling pathways involved in the malignant transformation of normal melanocytes to malignant melanoma.

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Section: Discussionmentioning

confidence: 99%

Section: Uv-induced Redox Imbalance Modulates Redox-sensitive Mirnasmentioning

confidence: 99%

Section: Uv-dysregulated Redox-sensitive Mirnas Involved In Melanoma ...mentioning

confidence: 99%

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Oxidative-Stress-Sensitive microRNAs in UV-Promoted Development of Melanoma

Pecorelli

Valacchi

2022

Cancers

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“…This adaptive metabolic program limits the efficacy of targeted-therapy and is one of the mechanisms responsible for adaptive resistance [ 26 , 27 , 28 , 29 , 30 , 146 ]. As a consequence of high mitochondrial activity, resistant cells show higher level of ROS, which can lead to a proliferative advantage [ 147 , 148 ]. In addition, amino acids biosynthetic pathways, including serine, glycine, and glutamine, may contribute to melanoma metabolic rewiring in melanoma [ 135 , 146 , 149 ], as well as the metabolic exchange within TME between melanoma and stromal/immune cells [ 31 ], even if less studied during the onset of resistance.…”

Section: Metabolic Plasticity In Melanoma Drives Resistancementioning

confidence: 99%

NAD/NAMPT and mTOR Pathways in Melanoma: Drivers of Drug Resistance and Prospective Therapeutic Targets

Indini

Fiorilla

Ponzone

et al. 2022

IJMS

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Malignant melanoma represents the most fatal skin cancer due to its aggressive behavior and high metastatic potential. The introduction of BRAF/MEK inhibitors and immune-checkpoint inhibitors (ICIs) in the clinic has dramatically improved patient survival over the last decade. However, many patients either display primary (i.e., innate) or develop secondary (i.e., acquired) resistance to systemic treatments. Therapeutic resistance relies on the rewiring of multiple processes, including cancer metabolism, epigenetics, gene expression, and interactions with the tumor microenvironment that are only partially understood. Therefore, reliable biomarkers of resistance or response, capable of facilitating the choice of the best treatment option for each patient, are currently missing. Recently, activation of nicotinamide adenine dinucleotide (NAD) metabolism and, in particular, of its rate-limiting enzyme nicotinamide phosphoribosyltransferase (NAMPT) have been identified as key drivers of targeted therapy resistance and melanoma progression. Another major player in this context is the mammalian target of rapamycin (mTOR) pathway, which plays key roles in the regulation of melanoma cell anabolic functions and energy metabolism at the switch between sensitivity and resistance to targeted therapy. In this review, we summarize known resistance mechanisms to ICIs and targeted therapy, focusing on metabolic adaptation as one main mechanism of drug resistance. In particular, we highlight the roles of NAD/NAMPT and mTOR signaling axes in this context and overview data in support of their inhibition as a promising strategy to overcome treatment resistance.

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“…Cells maintain ROS homeostasis through superoxide dismutase (SOD) system, catalase (CAT) system, glutathione peroxidase (GSH-Px) system, etc. ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Antioxidant Activity and the Potential Mechanism of the Fruit From Ailanthus altissima Swingle

Cheng

Yang

et al. 2021

Front. Vet. Sci.

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The fruits of Ailanthus altissima Swingle (AS) possess a variety of pharmacological activities. Its antioxidant activity and the potential mode of action have not yet been investigated. In in vitro studies, AS revealed the strong reducing power and DPPH scavenging effect, but hydroxyl radical scavenging activity and ferrous ions-chelating ability were not strong. Meanwhile, the oxidative stress RAW264.7 cell injury model was established, the low and medium-doses of AS showed significant protective effects on the viability of H2O2-treated cells by CCK-8 method. Besides, three doses of AS all increased the activities of SOD, CAT, and GSH-Px and decreased the MDA level compared with the H2O2 group, suggesting it significantly relieved oxidative stress of cells. The active ingredients and related targets of AS were collected by HERB and Swiss Target Prediction database, the common targets of drugs and diseases database were conducted by GeneCards database platform and the Venny platform. We screened the core targets of AS like threonine kinase1 (AKT1), mitogen-activated protein kinase 1 (MAPK1), sirtuin-1 (SIRT1), mechanistic target of rapamycin kinase (MTOR) by STRING database, and the key pathways involved PI3K-AKT and FoxO signaling pathway by KEGG pathway enrichment analysis. Besides, qRT-PCR revealed AS preconditioning significantly up-regulated the expression level of AKT1, SIRT1, MAPK1, and MTOR in model cells, and the effect was related to the regulation of FoxO and PI3K/AKT signaling pathway. In summary, AS showed significant antioxidant activity and its potential mechanism was regulating FoxO and PI3K/AKT signaling pathway.

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ROS as Regulators of Cellular Processes in Melanoma

Cited by 26 publications

References 207 publications

Oxidative-Stress-Sensitive microRNAs in UV-Promoted Development of Melanoma

Oxidative-Stress-Sensitive microRNAs in UV-Promoted Development of Melanoma

NAD/NAMPT and mTOR Pathways in Melanoma: Drivers of Drug Resistance and Prospective Therapeutic Targets

Antioxidant Activity and the Potential Mechanism of the Fruit From Ailanthus altissima Swingle

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