Special Issue "Role of MicroRNA in Cancer Development and Treatment"

A special issue of Journal of Personalized Medicine (ISSN 2075-4426).

Deadline for manuscript submissions: closed (5 October 2021).

Special Issue Editors

Prof. Dr. Alessandra Pulliero
E-Mail Website
Guest Editor
Department of Health Sciences, Faculty of Medicine and Surgery, University of Genoa, via Pastore 1, 16132 Genoa, Italy
Interests: lung cancer; microRNA; lung cancer microRNA in liquid biopsy
Prof. Dr. Alberto Izzotti
E-Mail Website
Guest Editor
Department of Experimental Medicine, University of Genoa, School of Medicine, University of Genoa; Director UOC Mutagenesis and Cancer Prevention, Comprehensive Cancer Center; Hospital Policlinico San Martino-IRCCS, Genoa, Italy.
Interests: microRNA; genotoxicity; DNA damage; mutagenicity; oxidative stress biomarkers; mutagenesis; antioxidant activity; oxidative stress; DNA repair; apoptosis

Special Issue Information

Dear Colleagues,

Background: Many researchers around the world have demonstrated that the expression of miRNAs is dysregulated in different tumors. Such dysregulation is caused by multiple mechanisms, and exposure to different carcinogens causes dysregulated epigenetic changes and defects in the miRNA biogenesis machinery.

Aim and scope: Cancer cells with abnormal miRNA expression evolve the capability to sustain proliferative signaling, evade growth suppressors, resist cell death, activate invasion and metastasis and induce angiogenesis. Genome-wide profiling demonstrates that miRNA expression signatures are associated with tumor type, tumor grade and clinical outcomes, so miRNAs could be potential candidates for diagnostic biomarkers, prognostic biomarkers, therapeutic targets and preventive screening programs. Although miRNAs have multiple targets, their function in tumorigenesis is due to their regulation of a few specific targets.

History: After the first detection of altered miRNA in leukemia, microRNAs have been demonstrated to be constantly altered in all cancer. More recently, microRNA has been shown to be altered by exposure to environmental carcinogens, thus driving the whole process of carcinogenesis.

Cutting-edge research: Our aim is to provide rigorous peer review and enable rapid publication of cutting-edge research on the role of microRNA in cancer prevention therapy to educate and inspire the scientific community worldwide.

Desired submission types: We welcome research articles, review articles and comprehensive reviews.

Prof. Dr. Alessandra Pulliero
Prof. Dr. Alberto Izzotti
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • microRNAs
  • cancer prevention
  • liquid biopsies
  • biomarkers
  • tumor suppressors or oncogenes
  • epigenetic changes and defects in miRNA biogenesis
  • altered miRNA expression in tumors
  • cancer prognosis

Published Papers (11 papers)

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Research

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Article
Extracellular Vesicle Enriched miR-625-3p Is Associated with Survival of Malignant Mesothelioma Patients
J. Pers. Med. 2021, 11(10), 1014; https://doi.org/10.3390/jpm11101014 (registering DOI) - 09 Oct 2021
Viewed by 183
Abstract
Malignant mesothelioma (MM) is characterized by poor prognosis and short survival. Extracellular vesicles (EVs) are membrane-bound particles released from cells into various body fluids, and their molecular composition reflects the characteristics of the origin cell. Blood EVs or their miRNA cargo might serve [...] Read more.
Malignant mesothelioma (MM) is characterized by poor prognosis and short survival. Extracellular vesicles (EVs) are membrane-bound particles released from cells into various body fluids, and their molecular composition reflects the characteristics of the origin cell. Blood EVs or their miRNA cargo might serve as new minimally invasive biomarkers that would enable earlier detection of MM or treatment outcome prediction. Our aim was to evaluate miRNAs enriched in serum EVs as potential prognostic biomarkers in MM patients in a pilot longitudinal study. EVs were isolated from serum samples obtained before and after treatment using ultracentrifugation on 20% sucrose cushion. Serum EV-enriched miR-103-3p, miR-126-3p and miR-625-3p were quantified using qPCR. After treatment, expression of miR-625-3p and miR-126-3p significantly increased in MM patients with poor treatment outcome (p = 0.012 and p = 0.036, respectively). A relative increase in miR-625-3p expression after treatment for more than 3.2% was associated with shorter progression-free survival (7.5 vs. 19.4 months, HR = 3.92, 95% CI = 1.20–12.80, p = 0.024) and overall survival (12.5 vs. 49.1 months, HR = 5.45, 95% CI = 1.06–28.11, p = 0.043) of MM patients. Bioinformatic analysis showed enrichment of 33 miR-625-3p targets in eight biological pathways. Serum EV-enriched miR-625-3p could therefore serve as a prognostic biomarker in MM and could contribute to a more personalized treatment. Full article
(This article belongs to the Special Issue Role of MicroRNA in Cancer Development and Treatment)
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Article
Identification by MicroRNA Analysis of Environmental Risk Factors Bearing Pathogenic Relevance in Non-Smoker Lung Cancer
J. Pers. Med. 2021, 11(7), 666; https://doi.org/10.3390/jpm11070666 - 15 Jul 2021
Cited by 1 | Viewed by 469
Abstract
MicroRNA and DNA adduct biomarkers may be used to identify the contribution of environmental pollution to some types of cancers. The aim of this study was to use integrated DNA adducts and microRNAs analyses to study retrospectively the contribution of exposures to environmental [...] Read more.
MicroRNA and DNA adduct biomarkers may be used to identify the contribution of environmental pollution to some types of cancers. The aim of this study was to use integrated DNA adducts and microRNAs analyses to study retrospectively the contribution of exposures to environmental carcinogens to lung cancer in 64 non-smokers living in Sicily and Catania city near to the Etna volcano. MicroRNAs were extracted from cancer lung biopsies, and from the surrounding lung normal tissue. The expression of 2549 human microRNAs was analyzed by microarray. Benzo(a)Pyrene-DNA adducts levels were analyzed in the patients’ blood by HPLC−fluorescence detection. Correlations between tetrols and environmental exposures were calculated using Pearson coefficients and regression variable plots. Compared with the healthy tissue, 273 microRNAs were downregulated in lung cancer. Tetrols levels were inversely related both with the distance from Etna and years since smoking cessation, but they were not significantly correlated to environmental exposures. The analysis of the microRNA environmental signatures indicates the contribution of environmental factors to the analyzed lung cancers in the following decreasing rank: (a) car traffic, (b) passive smoke, (c) radon, and (d) volcano ashes. These results provide evidence that microRNA analysis can be used to retrospectively investigate the contribution of environmental factors in human lung cancer occurring in non-smokers. Full article
(This article belongs to the Special Issue Role of MicroRNA in Cancer Development and Treatment)
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Article
MicroRNA Expression Profile Distinguishes Glioblastoma Stem Cells from Differentiated Tumor Cells
J. Pers. Med. 2021, 11(4), 264; https://doi.org/10.3390/jpm11040264 - 01 Apr 2021
Cited by 2 | Viewed by 652
Abstract
Glioblastoma (GBM) represents the most common and aggressive tumor of the brain. Despite the fact that several studies have recently addressed the molecular mechanisms underlying the disease, its etiology and pathogenesis are still poorly understood. GBM displays poor prognosis and its resistance to [...] Read more.
Glioblastoma (GBM) represents the most common and aggressive tumor of the brain. Despite the fact that several studies have recently addressed the molecular mechanisms underlying the disease, its etiology and pathogenesis are still poorly understood. GBM displays poor prognosis and its resistance to common therapeutic approaches makes it a highly recurrent tumor. Several studies have identified a subpopulation of tumor cells, known as GBM cancer stem cells (CSCs) characterized by the ability of self-renewal, tumor initiation and propagation. GBM CSCs have been shown to survive GBM chemotherapy and radiotherapy. Thus, targeting CSCs represents a promising approach to treat GBM. Recent evidence has shown that GBM is characterized by a dysregulated expression of microRNA (miRNAs). In this study we have investigated the difference between human GBM CSCs and their paired autologous differentiated tumor cells. Array-based profiling and quantitative Real-Time PCR (qRT-PCR) were performed to identify miRNAs differentially expressed in CSCs. The Cancer Genome Atlas (TCGA) data were also interrogated, and functional interpretation analysis was performed. We have identified 14 miRNAs significantly differentially expressed in GBM CSCs (p < 0.005). MiR-21 and miR-95 were among the most significantly deregulated miRNAs, and their expression was also associated to patient survival. We believe that the data provided here carry important implications for future studies aiming at elucidating the molecular mechanisms underlying GBM. Full article
(This article belongs to the Special Issue Role of MicroRNA in Cancer Development and Treatment)
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Article
Relationship between the miRNA Profiles and Oncogene Mutations in Non-Smoker Lung Cancer. Relevance for Lung Cancer Personalized Screenings and Treatments
J. Pers. Med. 2021, 11(3), 182; https://doi.org/10.3390/jpm11030182 - 05 Mar 2021
Cited by 3 | Viewed by 558
Abstract
Oncogene mutations may be drivers of the carcinogenesis process. MicroRNA (miRNA) alterations may be adaptive or pathogenic and can have consequences only when mutation in the controlled oncogenes occurs. The aim of this research was to analyze the interplay between miRNA expression and [...] Read more.
Oncogene mutations may be drivers of the carcinogenesis process. MicroRNA (miRNA) alterations may be adaptive or pathogenic and can have consequences only when mutation in the controlled oncogenes occurs. The aim of this research was to analyze the interplay between miRNA expression and oncogene mutation. A total of 2549 miRNAs were analyzed in cancer tissue—in surrounding normal lung tissue collected from 64 non-smoking patients and in blood plasma. Mutations in 92 hotspots of 22 oncogenes were tested in the lung cancer tissue. MicroRNA alterations were related to the mutations occurring in cancer patients. Conversely, the frequency of mutation occurrence was variable and spanned from the k-ras and p53 mutation detected in 30% of patients to 20% of patients in which no mutation was detected. The prediction of survival at a 3-year follow up did not occur for mutation analysis but was, conversely, well evident for miRNA analysis highlighting a pattern of miRNA distinguishing between survivors and death in patients 3 years before this clinical onset. A signature of six lung cancer specific miRNAs occurring both in the lungs and blood was identified. The obtained results provide evidence that the analysis of both miRNA and oncogene mutations was more informative than the oncogene mutation analysis currently performed in clinical practice. Full article
(This article belongs to the Special Issue Role of MicroRNA in Cancer Development and Treatment)
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Article
Potential Role of miRNAs in the Acquisition of Chemoresistance in Neuroblastoma
J. Pers. Med. 2021, 11(2), 107; https://doi.org/10.3390/jpm11020107 - 07 Feb 2021
Cited by 2 | Viewed by 675
Abstract
Neuroblastoma (NB) accounts for about 8–10% of pediatric cancers, and the main causes of death are the presence of metastases and the acquisition of chemoresistance. Metastatic NB is characterized by MYCN amplification that correlates with changes in the expression of miRNAs, which are [...] Read more.
Neuroblastoma (NB) accounts for about 8–10% of pediatric cancers, and the main causes of death are the presence of metastases and the acquisition of chemoresistance. Metastatic NB is characterized by MYCN amplification that correlates with changes in the expression of miRNAs, which are small non-coding RNA sequences, playing a crucial role in NB development and chemoresistance. In the present study, miRNA expression was analyzed in two human MYCN-amplified NB cell lines, one sensitive (HTLA-230) and one resistant to Etoposide (ER-HTLA), by microarray and RT-qPCR techniques. These analyses showed that miRNA-15a, -16-1, -19b, -218, and -338 were down-regulated in ER-HTLA cells. In order to validate the presence of this down-regulation in vivo, the expression of these miRNAs was analyzed in primary tumors, metastases, and bone marrow of therapy responder and non-responder pediatric patients. Principal component analysis data showed that the expression of miRNA-19b, -218, and -338 influenced metastases, and that the expression levels of all miRNAs analyzed were higher in therapy responders in respect to non-responders. Collectively, these findings suggest that these miRNAs might be involved in the regulation of the drug response, and could be employed for therapeutic purposes. Full article
(This article belongs to the Special Issue Role of MicroRNA in Cancer Development and Treatment)
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Article
miR-210 and miR-152 as Biomarkers by Liquid Biopsy in Invasive Ductal Carcinoma
J. Pers. Med. 2021, 11(1), 31; https://doi.org/10.3390/jpm11010031 - 06 Jan 2021
Viewed by 1125
Abstract
Detecting circulating microRNAs (miRNAs; miRs) by means of liquid biopsy is an important tool for the early diagnosis and prognosis of breast cancer (BC). We aimed to identify and validate miR-210 and miR-152 as non-invasive circulating biomarkers, for the diagnosis and staging of [...] Read more.
Detecting circulating microRNAs (miRNAs; miRs) by means of liquid biopsy is an important tool for the early diagnosis and prognosis of breast cancer (BC). We aimed to identify and validate miR-210 and miR-152 as non-invasive circulating biomarkers, for the diagnosis and staging of BC patients, confirming their involvement in tumor angiogenesis. Methods: RT-qPCR was performed and MiRNA expression analysis was obtained from plasma and fragments of BC and benign breast condition (BBC) women patients, plus healthy subjects. Additionally, the immunohistochemistry technique was carried out to analyze the expression of target proteins. Results: Tumor fragments showed increased expression of oncomiR-210 and decreased expression of miR-152 tumoral suppressor. Both miRNAs were increased in plasma samples from BC patients. The receiver operating characteristic (ROC) curve analysis revealed that only the expression of oncomiR-210 in tissue samples and only the expression of the miR-152 suppressor in plasma have the appropriate sensitivity and specificity for use as differential biomarkers between early/intermediate and advanced stages of BC patients. In addition, there was an increase in the expression of hypoxia-inducible factor 1-alpha (HIF-1α), insulin-like growth factor 1 receptor (IGF-1R), and vascular endothelial growth factor (VEGF) in BC patients. On the contrary, a decrease in Von Hippel–Lindau (VHL) protein expression was observed. Conclusions: This study showed that increased levels of miR-210 and decreased levels of miR152, in addition to the expressions of their target proteins, could indicate, respectively, the oncogenic and tumor suppressive role of these miRNAs in fragments. Both miRNAs are potential diagnostic biomarkers for BC by liquid biopsy. In addition, miR-152 proved to be a promising biomarker for disease staging. Full article
(This article belongs to the Special Issue Role of MicroRNA in Cancer Development and Treatment)
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Review

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Review
Oncogenic Role of miRNA in Environmental Exposure to Plasticizers: A Systematic Review
J. Pers. Med. 2021, 11(6), 500; https://doi.org/10.3390/jpm11060500 - 02 Jun 2021
Cited by 1 | Viewed by 708
Abstract
The daily environmental exposure of humans to plasticizers may adversely affect human health, representing a global issue. The altered expression of microRNAs (miRNAs) plays an important pathogenic role in exposure to plasticizers. This systematic review summarizes recent findings showing the modified expression of [...] Read more.
The daily environmental exposure of humans to plasticizers may adversely affect human health, representing a global issue. The altered expression of microRNAs (miRNAs) plays an important pathogenic role in exposure to plasticizers. This systematic review summarizes recent findings showing the modified expression of miRNAs in cancer due to exposure to plasticizers. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, we performed a systematic review of the literature published in the past 10 years, focusing on the relationship between plasticizer exposure and the expression of miRNAs related to cancer. Starting with 535 records, 17 articles were included. The results support the hypothesis that exposure to plasticizers causes changes in or the deregulation of a number of oncogenic miRNAs and show that the interaction of plasticizers with several redundant miRNAs, such as let-7f, let-7g, miR-125b, miR-134, miR-146a, miR-22, miR-192, miR-222, miR-26a, miR-26b, miR-27b, miR-296, miR-324, miR-335, miR-122, miR-23b, miR-200, miR-29a, and miR-21, might induce deep alterations. These genotoxic and oncogenic responses can eventually lead to abnormal cell signaling pathways and metabolic changes that participate in many overlapping cellular processes, and the evaluation of miRNA-level changes can be a useful target for the toxicological assessment of environmental pollutants, including plastic additives and plasticizers. Full article
(This article belongs to the Special Issue Role of MicroRNA in Cancer Development and Treatment)
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Review
Precision Medicine and Public Health: New Challenges for Effective and Sustainable Health
J. Pers. Med. 2021, 11(2), 135; https://doi.org/10.3390/jpm11020135 - 16 Feb 2021
Cited by 1 | Viewed by 1313
Abstract
The development of high-throughput omics technologies represents an unmissable opportunity for evidence-based prevention of adverse effects on human health. However, the applicability and access to multi-omics tests are limited. In Italy, this is due to the rapid increase of knowledge and the high [...] Read more.
The development of high-throughput omics technologies represents an unmissable opportunity for evidence-based prevention of adverse effects on human health. However, the applicability and access to multi-omics tests are limited. In Italy, this is due to the rapid increase of knowledge and the high levels of skill and economic investment initially necessary. The fields of human genetics and public health have highlighted the relevance of an implementation strategy at a national level in Italy, including integration in sanitary regulations and governance instruments. In this review, the emerging field of public health genomics is discussed, including the polygenic scores approach, epigenetic modulation, nutrigenomics, and microbiomes implications. Moreover, the Italian state of implementation is presented. The omics sciences have important implications for the prevention of both communicable and noncommunicable diseases, especially because they can be used to assess the health status during the whole course of life. An effective population health gain is possible if omics tools are implemented for each person after a preliminary assessment of effectiveness in the medium to long term. Full article
(This article belongs to the Special Issue Role of MicroRNA in Cancer Development and Treatment)
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Review
Salivary Micro-RNA and Oral Squamous Cell Carcinoma: A Systematic Review
J. Pers. Med. 2021, 11(2), 101; https://doi.org/10.3390/jpm11020101 - 04 Feb 2021
Cited by 2 | Viewed by 689
Abstract
Oral squamous cell carcinoma (OSCC) is a widespread malignancy with high mortality. In particular, a delay in its diagnosis dramatically decreases the survival rate. The aim of this systematic review was to investigate and summarize clinical results in the literature, regarding the potential [...] Read more.
Oral squamous cell carcinoma (OSCC) is a widespread malignancy with high mortality. In particular, a delay in its diagnosis dramatically decreases the survival rate. The aim of this systematic review was to investigate and summarize clinical results in the literature, regarding the potential use of salivary microRNAs (miRNAs) as diagnostic and prognostic biomarkers for OSCC patients. Twelve papers were selected, including both case–control and cohort studies, and all of them detected significantly dysregulated miRNAs in OSCC patients compared to healthy controls. Based on our results, salivary miRNAs might provide a non-invasive and cost-effective method in the diagnosis of OSCC, and also to monitor more easily its evolution and therapeutic response and therefore aid in the establishment of specific therapeutic strategies. Full article
(This article belongs to the Special Issue Role of MicroRNA in Cancer Development and Treatment)
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Review
Role of microRNAs in Lung Carcinogenesis Induced by Asbestos
J. Pers. Med. 2021, 11(2), 97; https://doi.org/10.3390/jpm11020097 - 03 Feb 2021
Cited by 1 | Viewed by 841
Abstract
MicroRNAs are a class of small noncoding endogenous RNAs 19–25 nucleotides long, which play an important role in the post-transcriptional regulation of gene expression by targeting mRNA targets with subsequent repression of translation. MicroRNAs are involved in the pathogenesis of numerous diseases, including [...] Read more.
MicroRNAs are a class of small noncoding endogenous RNAs 19–25 nucleotides long, which play an important role in the post-transcriptional regulation of gene expression by targeting mRNA targets with subsequent repression of translation. MicroRNAs are involved in the pathogenesis of numerous diseases, including cancer. Lung cancer is the leading cause of cancer death in the world. Lung cancer is usually associated with tobacco smoking. However, about 25% of lung cancer cases occur in people who have never smoked. According to the International Agency for Research on Cancer, asbestos has been classified as one of the cancerogenic factors for lung cancer. The mechanism of malignant transformation under the influence of asbestos is associated with the genotoxic effect of reactive oxygen species, which initiate the processes of DNA damage in the cell. However, epigenetic mechanisms such as changes in the microRNA expression profile may also be implicated in the pathogenesis of asbestos-induced lung cancer. Numerous studies have shown that microRNAs can serve as a biomarker of the effects of various adverse environmental factors on the human body. This review examines the role of microRNAs, the expression profile of which changes upon exposure to asbestos, in key processes of carcinogenesis, such as proliferation, cell survival, metastasis, neo-angiogenesis, and immune response avoidance. Full article
(This article belongs to the Special Issue Role of MicroRNA in Cancer Development and Treatment)
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Review
The Impact of Air Pollution Exposure on the MicroRNA Machinery and Lung Cancer Development
J. Pers. Med. 2021, 11(1), 60; https://doi.org/10.3390/jpm11010060 - 19 Jan 2021
Cited by 1 | Viewed by 1032
Abstract
Small non-coding RNA molecules (miRNAs) play an important role in the epigenetic regulation of gene expression. As these molecules have been repeatedly implicated in human cancers, they have been suggested as biomarkers of the disease. Additionally, miRNA levels have been shown to be [...] Read more.
Small non-coding RNA molecules (miRNAs) play an important role in the epigenetic regulation of gene expression. As these molecules have been repeatedly implicated in human cancers, they have been suggested as biomarkers of the disease. Additionally, miRNA levels have been shown to be affected by environmental pollutants, including airborne contaminants. In this review, we searched the current literature for miRNAs involved in lung cancer, as well as miRNAs deregulated as a result of exposure to air pollutants. We then performed a synthesis of the data and identified those molecules commonly deregulated under both conditions. We detected a total of 25 miRNAs meeting the criteria, among them, miR-222, miR-21, miR-126-3p, miR-155 and miR-425 being the most prominent. We propose these miRNAs as biomarkers of choice for the identification of human populations exposed to air pollution with a significant risk of developing lung cancer. Full article
(This article belongs to the Special Issue Role of MicroRNA in Cancer Development and Treatment)
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