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

Exposure to environmental contaminants may lead to changes in the expression of microRNAs (miRNAs), resulting in several health effects [...]

Physical activity and cancer prevention: a review of current evidence and biological mechanisms

Objective. The main aim of this paper is to review the evidence available from the date of PubMed?s inception to May 2011 for a link between cancer and physical activity (PA) in both animal models and humans. Methods. We decided to select studies that comply with the scheme proposed by the American College of Sports Medicine/ American Heart Association (ACSM/AHA) that distinguish occupational physical activity (OPA) and leisure-time physical activity (LT-PA), further classified in three levels of intensity (low, moderate and heavy) based on the Metabolic Equivalent of Task (MET) index. Results. Considering animal models, there was strong evidence for an inverse association between voluntary wheel exercise and the risk of colon and breast cancer. Regarding human studies, we identified the following main results: 1) colorectum: LT-PA provided an overall colon risk reduction of 13-14%; 2) breast: significant reduction in the frequency of post-menopausal (PMP) cancers in women that practiced heavy and moderate LT-PA; 3) prostate: heavy OPA and LT-PA seemed to reduce the risk of advanced prostate cancers; 4) endometrium: strong protective effect of heavy/moderate LT-PA among overweight/ obese women; 5) lung: inverse relationship between heavy LT-PA and lung cancer in former or current smokers across all histologies. Conclusion. Increased LT-PA is associated with cancer prevention in several organs, but strong biases, such as body mass index (BMI), gender and age, make it difficult to assess which aspects of PA contribute most strongly to the reduced risk. Furthermore, we found few studies that indicated a protective role for OPA in cancer prevention when compared with LT-PA

Analysis of nestin protein in the aqueous humor as biomarker of open angle glaucoma

Primary open angle glaucoma (POAG) is a progressive optic nerve degeneration, leading to irreversible visual damage. Alterations of the aqueous humor (AH), the biological fluid filling both the anterior and the posterior chambers of the eye, play a pathogenic role in POAG. AH protein composition is altered during glaucoma progression. Nestin protein was found to be differentially expressed in the AH of glaucomatous patients compared to unaffected matched controls

MicroRNA Alterations Induced in Human Skin by Diesel Fumes, Ozone, and UV Radiation

Epigenetic alterations are a driving force of the carcinogenesis process. MicroRNAs play a role in silencing mutated oncogenes, thus defending the cell against the adverse consequences of genotoxic damages induced by environmental pollutants. These processes have been well investigated in lungs; however, although skin is directly exposed to a great variety of environmental pollutants, more research is needed to better understand the effect on cutaneous tissue. Therefore, we investigated microRNA alteration in human skin biopsies exposed to diesel fumes, ozone, and UV light for over 24 h of exposure. UV and ozone-induced microRNA alteration right after exposure, while the peak of their deregulations induced by diesel fumes was reached only at the end of the 24 h. Diesel fumes mainly altered microRNAs involved in the carcinogenesis process, ozone in apoptosis, and UV in DNA repair. Accordingly, each tested pollutant induced a specific pattern of microRNA alteration in skin related to the intrinsic mechanisms activated by the specific pollutant. These alterations, over a short time basis, reflect adaptive events aimed at defending the tissue against damages. Conversely, whenever environmental exposure lasts for a long time, the irreversible alteration of the microRNA machinery results in epigenetic damage contributing to the pathogenesis of inflammation, dysplasia, and cancer induced by environmental pollutants

Small RNAs in eucaryotes: new clues for amplifying microRNA benefits

miRNAs, the smallest nucleotide molecules able to regulate gene expression at post transcriptional level, are found in both animals and plants being involved in fundamental processes for growth and development of living organisms. The number of miRNAs has been hypothesized to increase when some organisms specialized the process of mastication and grinding of food. Further to the vertical transmission, miRNAs can undergo horizontal transmission among different species, in particular between plants and animals. In the last years, an increasing number of studies reported that miRNA passage occurs through feeding, and that in animals, plant miRNAs can survive the gastro intestinal digestion and transferred by blood into host cells, where they can exert their functions modulating gene expression. The present review reports studies on miRNAs during evolution, with particular focus on biogenesis and mechanisms regulating their stability in plants and animals. The different biogenesis and post biogenesis modifications allow to discriminate miRNAs of plant origin from those of animal origin, and make it possible to better clarify the controversial question on whether a possible cross-kingdom miRNA transfer through food does exist. The majority of human medicines and supplements derive from plants and a regular consumption of plant food is suggested for their beneficial effects in the prevention of metabolic diseases, cancers, and dietary related disorders. So far, these beneficial effects have been generally attributed to the content of secondary metabolites, whereas mechanisms regarding other components remain unclear. Therefore, in light of the above reported studies miRNAs could result another component for the medical properties of plants. miRNAs have been mainly studied in mammals characterizing their sequences and molecular targets as available in public databases. The herein presented studies provide evidences that miRNA situation is much more complex than the static situation reported in databases. Indeed, miRNAs may have redundant activities, variable sequences, different methods of biogenesis, and may be differently influenced by external and environmental factors. In-depth knowledge of mechanisms of synthesis, regulation and transfer of plant miRNAs to other species can open new frontiers in the therapy of many human diseases, including cancer

MiR\u201119 in blood plasma reflects lung cancer occurrence but is not specifically associated with radon exposure

Radon is one of the most powerful carcinogens, particularly in terms of lung cancer onset and development. miRNAs may be considered not only as markers of the ongoing tumorigenesis but also as a hallmark of exposure to radiation, including radon and its progeny. Therefore, the purpose of the present study was to estimate the value of plasma miR\u201119b\u20113p level as the prospective marker of the response to radon exposure in lung cancer pathogenesis. A total of 136 subjects were examined, including 49 radon\u2011exposed patients with lung cancer, 37 patients with lung cancer without radon exposure and 50 age/sex matched healthy controls. Total RNA from blood samples was extracted and used to detect miR\u201119b\u20113p expression via reverse transcription quantitative\u2011polymerase chain reaction. The 2\u2011\u394\u394Cqmethod was used to quantify the amount of relative miRNA. The plasma level of p53 protein was determined using a Human p53 ELISA kit. Plasma miR\u201119b\u20113p level was significantly higher in the patients with lung cancer groups, compared with the healthy control group (P<0.0001). No other statistically significant differences were determined in the expression level of plasma miR\u201119b\u20113p between patients diagnosed with lung cancer exposed to radon and not exposed to radon. The expression level of free circulating miR\u201119b\u20113p was higher in the group of non\u2011smoking patients with lung cancer, compared with smokers with lung cancer. The miR\u201119b\u20113p was 1.4\u2011fold higher in non\u2011smokers than in smokers (P<0.05). No association between plasma levels of p53 protein and miR\u201119b\u20113p freely circulating in patients with lung cancer was observed. No other statistically significant differences were determined in the plasma p53 protein level between patients diagnosed with lung cancer exposed and not exposed to radon. These results indicated that detection of miR\u201119b\u20113p levels in plasma potentially could be exploited as a noninvasive method for the lung cancer diagnostics. However, this miRNA is not suitable as the precise marker for radon impact

The Interaction among Microbiota, Epigenetic Regulation, and Air Pollutants in Disease Prevention

open6noEnvironmental pollutants can influence microbiota variety, with important implications for the general wellbeing of organisms. In subjects at high-risk of cancer, gut, and lung microbiota are distinct from those of low-risk subjects, and disease progression is associated with microbiota alterations. As with many inflammatory diseases, it is the combination of specific host and environmental factors in certain individuals that provokes disease outcomes. The microbiota metabolites influence activity of epigenetic enzymes. The knowledge of the mechanisms of action of environmental pollution now includes not only the alteration of the gut microbiota but also the interaction between different human microbiota niches such as the lung–gut axis. The epigenetic regulations can reprogram differentiated cells in response to environmental changes. The microbiota can play a major role in the progression and suppression of several epigenetic diseases. Accordingly, the maintenance of a balanced microbiota by monitoring the environmental stimuli provides a novel preventive approach for disease prevention. Metagenomics technologies can be utilized to establish new mitigation approaches for diseases induced by polluted environments. The purpose of this review is to examine the effects of particulate matter exposure on the progression of disease outcomes as related to the alterations of gut and lung microbial communities and consequent epigenetic modificationsopenAlessandra Pulliero, Deborah Traversi, Elena Franchitti, Martina Barchitta, Alberto Izzotti, Antonella AgodiPulliero, Alessandra; Traversi, Deborah; Franchitti, Elena; Barchitta, Martina; Izzotti, Alberto; Agodi, Antonell

The Role of Mitochondrial miRNAs in the Development of Radon-Induced Lung Cancer

MicroRNAs are short, non-coding RNA molecules regulating gene expression by inhibiting the translation of messenger RNA (mRNA) or leading to degradation. The miRNAs are encoded in the nuclear genome and exported to the cytosol. However, miRNAs have been found in mitochondria and are probably derived from mitochondrial DNA. These miRNAs are able to directly regulate mitochondrial genes and mitochondrial activity. Mitochondrial dysfunction is the cause of many diseases, including cancer. In this review, we consider the role of mitochondrial miRNAs in the pathogenesis of lung cancer with particular reference to radon exposure