Epigenetic Regulation of miRNA Expression in Malignant Mesothelioma: miRNAs as Biomarkers of Early Diagnosis and Therapy

Tomasetti, Marco; Gaetani, Simona; Monaco, Francesca Roversi; Neužil, Jiřı́; Santarelli, Lory

doi:10.3389/fonc.2019.01293

Cited by 40 publications

(38 citation statements)

References 135 publications

(148 reference statements)

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“…Early alterations in these molecular pathways can contribute to physiological and pathological changes in persons with diabetes [ 238 ]. Epigenetic alterations are in part responsible for insulin resistance development and therefore they are associated with the development of related complications [ 14 , 239 ].…”

Section: Discussionmentioning

confidence: 99%

“…This suggests that miRNA expression and function may be altered long before hyperglycemia is diagnosed, causing important changes in metabolism from an early stage. Furthermore, microRNAs (miRNAs) are not only important epigenetic regulators of metabolism [ 12 ], but the expression of these key molecules can also be highly regulated by epigenetic modifications, including histone modifications and DNA methylation [ 13 , 14 , 15 ]. Therefore, it is important to uncover these early changes in miRNA expression in order to best target for treatment those at the highest risk.…”

Section: Introductionmentioning

confidence: 99%

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Mechanistic Actions of microRNAs in Diabetic Wound Healing

Petković

Sørensen

Leal

et al. 2020

Cells

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Wound healing is a complex biological process that is impaired under diabetes conditions. Chronic non-healing wounds in diabetes are some of the most expensive healthcare expenditures worldwide. Early diagnosis and efficacious treatment strategies are needed. microRNAs (miRNAs), a class of 18–25 nucleotide long RNAs, are important regulatory molecules involved in gene expression regulation and in the repression of translation, controlling protein expression in health and disease. Recently, miRNAs have emerged as critical players in impaired wound healing and could be targets for potential therapies for non-healing wounds. Here, we review and discuss the mechanistic background of miRNA actions in chronic wounds that can shed the light on their utilization as specific wound healing biomarkers.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mechanistic Actions of microRNAs in Diabetic Wound Healing

Petković

Sørensen

Leal

et al. 2020

Cells

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“…Large-scale gene expression analysis evidence that the expression of individual miRNA or miRNA signatures will become routine biomarkers for cancer diagnosis and prognosis, and personalized therapy, thanks to their accessibility, high specificity, and sensitivity. miRNAs induce epigenetic alterations that are reversible and targeted multiple regulators of related pathways (274)(275)(276)(277). Tumor angiogenesis can be ruled by derepressing/miming tumor suppressor genes with angiostatic properties that are instead epigenetically silenced in a tumor, endothelial, and/or microenvironment cells, or by repressing oncogenes codifying for pro-angiogenic molecules (278,279).…”

Section: Challenges and Future Directionsmentioning

confidence: 99%

microRNAs Biogenesis, Functions and Role in Tumor Angiogenesis

et al. 2020

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microRNAs (miRNAs) are small non-coding RNA molecules, evolutionary conserved. They target more than one mRNAs, thus influencing multiple molecular pathways, but also mRNAs may bind to a variety of miRNAs, either simultaneously or in a context-dependent manner. miRNAs biogenesis, including miRNA transcription, processing by Drosha and Dicer, transportation, RISC biding, and miRNA decay, are finely controlled in space and time.miRNAs are critical regulators in various biological processes, such as differentiation, proliferation, apoptosis, and development in both health and disease. Their dysregulation is involved in tumor initiation and progression. In tumors, they can act as onco-miRNAs or oncosuppressor-miRNA participating in distinct cellular pathways, and the same miRNA can perform both activities depending on the context.In tumor progression, the angiogenic switch is fundamental. miRNAs derived from tumor cells, endothelial cells, and cells of the surrounding microenvironment regulate tumor angiogenesis, acting as pro-angiomiR or anti-angiomiR.In this review, we described miRNA biogenesis and function, and we update the non-classical aspects of them. The most recent role in the nucleus, as transcriptional gene regulators and the different mechanisms by which they could be dysregulated, in tumor initiation and progression, are treated. In particular, we describe the role of miRNAs in sprouting angiogenesis, vessel co-option, and vasculogenic mimicry. The role of miRNAs in lymphoma angiogenesis is also discussed despite the scarcity of data.The information presented in this review reveals the need to do much more to discover the complete miRNA network regulating angiogenesis, not only using high-throughput computational analysis approaches but also morphological ones.

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“…It is also imperative to include analyses of non-coding regions of the DNA, such as miRNA. While epigenetic alterations during oncogenesis directly affect the transcription of coding genes, these variations can have an effect on the expression of miRNAs ( 172 , 173 ), which are non-coding RNAs that function in RNA silencing and post-transcriptional regulation of gene expression. miRNAs can mediate either tumor suppressive or oncogenic effects depending on their gene target ( 174 ).…”

Section: Discussionmentioning

confidence: 99%

Understanding the Mechanisms by Which Epigenetic Modifiers Avert Therapy Resistance in Cancer

2020

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The development of resistance to anti-cancer therapeutics remains one of the core issues preventing the improvement of survival rates in cancer. Therapy resistance can arise in a multitude of ways, including the accumulation of epigenetic alterations in cancer cells. By remodeling DNA methylation patterns or modifying histone proteins during oncogenesis, cancer cells reorient their epigenomic landscapes in order to aggressively resist anti-cancer therapy. To combat these chemoresistant effects, epigenetic modifiers such as DNA hypomethylating agents, histone deacetylase inhibitors, histone demethylase inhibitors, along with others have been used. While these modifiers have achieved moderate success when used either alone or in combination with one another, the most positive outcomes were achieved when they were used in conjunction with conventional anti-cancer therapies. Epigenome modifying drugs have succeeded in sensitizing cancer cells to anti-cancer therapy via a variety of mechanisms: disrupting pro-survival/anti-apoptotic signaling, restoring cell cycle control and preventing DNA damage repair, suppressing immune system evasion, regulating altered metabolism, disengaging pro-survival microenvironmental interactions and increasing protein expression for targeted therapies. In this review, we explore different mechanisms by which epigenetic modifiers induce sensitivity to anti-cancer therapies and encourage the further identification of the specific genes involved with sensitization to facilitate development of clinical trials.

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Epigenetic Regulation of miRNA Expression in Malignant Mesothelioma: miRNAs as Biomarkers of Early Diagnosis and Therapy

Cited by 40 publications

References 135 publications

Mechanistic Actions of microRNAs in Diabetic Wound Healing

Mechanistic Actions of microRNAs in Diabetic Wound Healing

microRNAs Biogenesis, Functions and Role in Tumor Angiogenesis

Understanding the Mechanisms by Which Epigenetic Modifiers Avert Therapy Resistance in Cancer

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