Estrogen Repression of MicroRNAs Is Associated with High Guanine Content in the Terminal Loop Sequences of Their Precursors

Cohen, Amit; Burgos-Aceves, Mario Alberto; Kahan, Tamar; Smith, Yoav

doi:10.3390/biomedicines5030047

Cited by 8 publications

(8 citation statements)

References 51 publications

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“…The results presented here support previous studies showing the potential importance of TL-G content to the regulation of miRNAs expression and function [19][20][21][22]. We have previously suggested that estrogens metabolites inside the lungs, as a result of CS exposure, can potentially cause the observed widespread downregulation of miRNA expression, and contribute to lung tumor development [27,28].…”

Section: Discussionsupporting

confidence: 90%

“…Repressed miRNAs in lung and breast cancers were shown to be the most enriched in TLs G [22], and the relation of estrogen to the development of these types of cancer is well documented [27,30,31]. Furthermore, like in the current study, also in the aforementioned studies, dual GG enrichment in miRNA TLs was even more pronounced [20][21][22]. Remarkably, experimental studies have shown that sequences with repeated G bases (GG or GGG) show higher reactivity toward oxidation than isolated G bases [32].…”

Section: Discussionsupporting

confidence: 79%

“…The copyright holder for this preprint (which this version posted February 15, 2019. ; https://doi.org/10.1101/518472 doi: bioRxiv preprint Izzotti and Pulliero showed in their study that the G content of the TLs of miRNAs, which are involved in stress response, is higher than the G content of the other miRNAs [20]. We have recently found, using bioinformatic data analysis of zebrafish, mouse, and human breast cancer cell line, an association between the widespread miRNAs reduction that is observed after estrogen (17β-estradiol; E2) exposure and a high TL-G content in their precursors [21]. In addition, we also showed that similar G enrichment exists in TLs of downregulated miRNAs found in different human cancers [22].…”

Section: Introductionmentioning

confidence: 99%

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Guanine Content of MicroRNAs is Associated with their Tumor- Suppressive and Oncogenic Roles in Lung and Breast Cancers

Cohen

Burgos-Aceves

Smith

2021

MIRNA

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Background: microRNAs (miRNAs, miRs) are small noncoding RNAs that negatively regulate gene expression at the post-transcriptional level and fine-tune gene functions. A global repression of miRNAs expression in different types of human tumors, after exposure to cigarette-smoke, or to the hormone estrogen, have been shown to be associated with guanine (G) enrichment in the terminal loops (TLs) of their precursors. Methods: we integrated the G content of miRNA mature forms and precursor miRNA TLs with their described function in the literature, using the PubMed database. Gene Ontology term analysis was used to describe the pathways in which the G-enriched miRNA targets are involved. Results : herein we show an association between the relative G enrichment of precursor miRNAs’ TLs and their tendency to act as tumor suppressor miRs in human lung and breast cancers. Another association was observed between the high G content of the miRNAs 5-mature forms and their tendency to act as oncomiRs. Conclusion: the results support previous findings showing that the G sequence content is an important feature determining miRNA expression and function, and opens the way for future cancer investigations in this direction.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

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Guanine Content of MicroRNAs is Associated with their Tumor- Suppressive and Oncogenic Roles in Lung and Breast Cancers

Cohen

Burgos-Aceves

Smith

2021

MIRNA

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“…Thirdly, an a priori understanding of genetic background and physiological states is equally warranted, as specific teleost strains (Burgerhout et al, 2017) or endogenous factors may factors regulate epigenetic marks in addition to environmental factors (Figure 1). The importance of endogenous factors is exemplified by the estrogen-dependent regulation of the abundant and liver specific miRNA-122 in zebrafish (Cohen and Smith, 2014;Cohen et al, 2017), which may introduce sex-specific functional differences in the nutritional regulation and metabolic function of miRNA-122 in fish (Mennigen et al, 2015). Indeed, widespread sexually dimorphic miRNA expression profiles have been identified in developing zebrafish (Vaz et al, 2015), emphasizing that genetic or endogenous endocrine signals contribute to environmental regulation of epigenetic marks in teleost fish.…”

Section: A C C E P T E D Mmentioning

confidence: 99%

Epigenetics in teleost fish: From molecular mechanisms to physiological phenotypes

Best

Ikert

Kostyniuk

et al. 2018

Comparative Biochemistry and Physiology Part B: Biochemistry an

118

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While the field of epigenetics is increasingly recognized to contribute to the emergence of phenotypes in mammalian research models across different developmental and generational timescales, the comparative biology of epigenetics in the large and physiologically diverse vertebrate infraclass of teleost fish remains comparatively understudied. The cypriniform zebrafish and the salmoniform rainbow trout and Atlantic salmon represent two especially important teleost orders, because they offer the unique possibility to comparatively investigate the role of epigenetic regulation in 3R and 4R duplicated genomes. In addition to their sequenced genomes, these teleost species are well-characterized model species for development and physiology, and therefore allow for an investigation of the role of epigenetic modifications in the emergence of physiological phenotypes during an organism's lifespan and in subsequent generations. This review aims firstly to describe the evolution of the repertoire of genes involved in key molecular epigenetic pathways including histone modifications, DNA methylation and microRNAs in zebrafish, rainbow trout, and Atlantic salmon, and secondly, to discuss recent advances in research highlighting a role for molecular epigenetics in shaping physiological phenotypes in these and other teleost models. Finally, by discussing themes and current limitations of the emerging field of teleost epigenetics from both theoretical and technical points of view, we will highlight future research needs and discuss how epigenetics will not only help address basic research questions in comparative teleost physiology, but also inform translational research including aquaculture, aquatic toxicology, and human disease.

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“…miRNA, discovered in the late 20th century, is a unique class of small RNAs derived from the non-coding DNA regions of a gene, such as intron, and 5'- and 3'-untranslated region (UTRs), which play multiple roles in cell regulation, including proliferation, differentiation, and apoptosis. Expression of this class of RNA is tightly regulated by environmental conditions, including temperature, ( 6 ) pressure, ( 7 ) hormones, ( 8 ) endotoxins ( 9 ) and environmental toxins, ( 10 ) to maintain homeostasis. Several recent studies have revealed that some phytochemicals modulate miRNA expression to exhibit their physiological functions.…”

Section: Biological Functions and Recently Identified Mechanismsmentioning

confidence: 99%

Non-specific protein modifications may be novel mechanism underlying bioactive phytochemicals

Murakami

2018

J. Clin. Biochem. Nutr.

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In a variety of experimental models, dietary phytochemicals have been demonstrated to exhibit pronounced and versatile bioactivities. Importantly, the possibility of such phytochemicals for human application has been supported in part by epidemiological surveys, which have demonstrated that frequent ingestion of vegetables and fruits containing abundant phytochemicals lowers the risk of onset of various diseases. However, the action mechanisms underlying those dietary phytochemical activities remain to be fully elucidated. For example, even though the anti-oxidant effects of natural polyphenols have long received widespread attention from food scientists, their roles in and contribution to those bioactivities remain controversial because of their poor bioavailability, resulting in extremely low concentrations in the bloodstream. Meanwhile, another important question is why phytochemicals have beneficial effects for animals, including humans, since they are biosynthesized by plants as compounds necessary for adaptation to environmental stress. In regard to that fundamental question, we recently reported novel and unique mechanisms of action of zerumbone, a sesquiterpene with anti-inflammatory and chemopreventive properties. This agent was found to partially exhibit bioactivity through its non-specific interactions with cellular proteins. More strikingly, a non-specific protein binding action of zerumbone was revealed to partially contribute to its anti-inflammatory functions via activation of heat shock factor 1. The present review article highlights and introduces our recent findings regarding the proteo-stress-mediated mechanisms of this phytochemical, along with the concept of hormesis.

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Estrogen Repression of MicroRNAs Is Associated with High Guanine Content in the Terminal Loop Sequences of Their Precursors

Cited by 8 publications

References 51 publications

Guanine Content of MicroRNAs is Associated with their Tumor- Suppressive and Oncogenic Roles in Lung and Breast Cancers

Guanine Content of MicroRNAs is Associated with their Tumor- Suppressive and Oncogenic Roles in Lung and Breast Cancers

Epigenetics in teleost fish: From molecular mechanisms to physiological phenotypes

Non-specific protein modifications may be novel mechanism underlying bioactive phytochemicals

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