Mutual regulation of microRNAs and DNA methylation in human cancers

Wang, Sumei; Wu, Wanyin; Claret, François X.

doi:10.1080/15592294.2016.1273308

Cited by 123 publications

(96 citation statements)

References 126 publications

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“…However, NNK-induced DNA methylation can, at the same time, modulate miRNA levels by regulating MMR gene expression. Hypo-or hyper-methylation of miRNA was considered to represent a new level of complexity in gene regulation in human cancers [81], suggesting miR-21 or miR-155 promoter hypo-methylation [81][82][83][84] and miR-422a hyper-methylation, as previously reported for miR-373 [81,85], as potential epigenetic modifications caused by tobacco carcinogenic effects on MMR. On the other hand, alkylating agents, such as NNK can also directly or after biological activation react and form covalent bonds with nucleophilic centers found in DNA and RNA and proteins [86], supporting possible direct interference of NNK with levels of miRNAs, thereby causing their deregulation [48,49,[51][52][53][54].…”

Section: Discussionmentioning

confidence: 67%

“…On the other hand, alkylating agents, such as NNK can also directly or after biological activation react and form covalent bonds with nucleophilic centers found in DNA and RNA and proteins [86], supporting possible direct interference of NNK with levels of miRNAs, thereby causing their deregulation [48,49,[51][52][53][54]. Subsequently, NNK-induced miRNA deregulations can affect MMR gene expression, either thought post-transcriptional modifications or through DNA methylation by targeting DNA methyltransferases or methylation-related proteins [81].…”

Section: Discussionmentioning

confidence: 99%

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The Effect of NNK, A Tobacco Smoke Carcinogen, on the miRNA and Mismatch DNA Repair Expression Profiles in Lung and Head and Neck Squamous Cancer Cells

Doukas

Vageli²,

Lazopoulos

et al. 2020

Cells

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Tobacco smoking is a common risk factor for lung cancer and head and neck cancer. Molecular changes such as deregulation of miRNA expression have been linked to tobacco smoking in both types of cancer. Dysfunction of the Mismatch DNA repair (MMR) mechanism has also been associated with a poor prognosis of these cancers, while a cross-talk between specific miRNAs and MMR genes has been previously proposed. We hypothesized that exposure of lung and head and neck squamous cancer cells (NCI and FaDu, respectively) to tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is capable of altering the expression of MSH2 and MLH1, key MMR components, by promoting specific miRNA deregulation. We found that either a low (1 µM) or high (2 µM) dose of NNK induced significant upregulation of "oncomirs" miR-21 and miR-155 and downregulation of "tumor suppressor" miR-422a, as well as the reduction of MMR protein and mRNA expression, in NCI and FaDu, compared to controls. Inhibition of miR-21 restored the NNK-induced reduced MSH2 phenotype in both NCI and FaDu, indicating that miR-21 might contribute to MSH2 regulation. Finally, NNK exposure increased NCI and FaDu survival, promoting cancer cell progression. We provide novel findings that deregulated miR-21, miR-155, and miR-422a and MMR gene expression patterns may be valuable biomarkers for lung and head and neck squamous cell cancer progression in smokers.Cells 2020, 9, 1031 2 of 22 and neck squamous cell carcinoma (HNSCC), represents one of the most aggressive malignancies with a high rate of mortality. [8,9]. Tobacco smoking has been one of the most well-established risk factors for both lung and head and neck cancers [1][2][3][4][5][6][7][8]. It is known that tobacco smoke contains a mixture of thousands of compounds, including a large number of known carcinogens [2]. It is believed that exposure of cells to tobacco smoke carcinogens can lead to DNA damage, which may cause chromosomal instability and increased cell proliferation [10][11][12][13]. In particular, tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which is one of the chemicals in tobacco smoke, has been linked to lung and head and neck cancer [14], and has also been shown to upregulate oncogenic pathways [15][16][17].The development and progression of lung and head and neck malignancies appear to be a complex process. Although multiple diagnostic and prognostic markers have been identified for both lung and head and neck cancers [18,19], the precise molecular mechanisms involved in the development and progression of these malignancies remain unclear.We understand that a functional DNA repair mechanism that includes the recognition and repair of mismatch DNA errors during DNA replication is essential in eliminating the harmful effect of several environmental risk factors, such as NNK, on the exposed cells [20][21][22][23]. A number of studies have shown that reduced expression of mismatch DNA repair (MMR) genes increases the incidence of microsatellite ...

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

The Effect of NNK, A Tobacco Smoke Carcinogen, on the miRNA and Mismatch DNA Repair Expression Profiles in Lung and Head and Neck Squamous Cancer Cells

Doukas

Vageli²,

Lazopoulos

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…DNA methylation can result in the inhibition or activation of miRNA transcription by hypermethylating or hypomethylating the CpG islands in the promoter regions of miRNAs. Conversely, miRNAs can also regulate DNA methylation by directly targeting DNA methyltransferases and methylation-related critical proteins, thereby affecting the whole genome methylation pattern [14]. It is worth noting that DNMT1 was predicted to be a target gene of three DEmiRs including miR-126-3p, miR-18a-5p and miR-429.…”

Section: Discussionmentioning

confidence: 99%

“…DNA methylation regulates miRNA transcription by hyper-/hypo-methylating the promoter regions of miRNAs. Meanwhile, miRNAs can regulate genome-wide DNA methylation patterns by directly targeting DNA methyltransferases and methylation-related critical proteins [13,14].…”

Section: Introductionmentioning

confidence: 99%

Identification of Epigenetic Interactions between MicroRNA and DNA Methylation Associated with Polycystic Ovarian Syndrome

Mao¹,

Li²,

Zhao³

et al. 2019

Preprint

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Aberration in microRNA (miRNA) expression or DNA methylation is a causal factor for polycystic ovarian syndrome (PCOS), a common endocrine disorder and leading cause of infertility. However, the epigenetic interactions between miRNA and DNA methylation remain unexplored in PCOS. In this study, we conducted an integrated analysis of RNA-seq, miRNA-seq and MBD-seq on ovarian granulosa cells of PCOS and control groups to reveal the epigenetic interactions involved in the pathogenesis of PCOS. Firstly, we identified 830 genes and 30 miRNAs that were expressed differently in PCOS, and seven miRNAs were found to negatively regulate targeted mRNA expression. Next, in total, 130 miRNAs were found to be significantly differently methylated in promoter regions, while 13 were found to be associated with miRNA expression. Furthermore, the promoter hypermethylation of miR-429, miR-141-3p, and miR-126-3p was proven to suppress miRNA expression and therefore upregulate their corresponding genes, including XIAP, BRD3, MAPK14 and SLC7A5. Our results demonstrate that DNA methylation regulates miRNA expression and therefore controls its corresponding gene expression. The reactivation of the transcription of epigenetically silenced genes may be one of the key elements in PCOS pathogenesis. Meanwhile, the epigenetic mechanisms underlying the regulation of miRNA expression can provide a potential therapeutic target for PCOS in the future.

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“…The DAG in figure 2A evaluates the portion of the effect of early life socioeconomic conditions (exposure) on adult inflammatory levels (outcome) transmitted by intracellular processes regulating transcription of genes in immune cells (mediators). This "indirect" effect captures all potential pre-and post-transcriptional regulating mechanisms including DNA methylation, histone modifications, transcription factors binding and microRNAs 30,31 . These processes mutually regulate in both physiological and diseases conditions.…”

Section: Causal Models and Measuresmentioning

confidence: 99%

Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two European cohort studies

Carmeli

Kutalik

Mishra

et al. 2020

Preprint

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Individuals growing up during childhood in a socioeconomically disadvantaged family experience a higher rate of inflammation-related diseases later in life. Little is known about the mechanisms linking early life experiences to the functioning of the immune system decades later. Here we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation (C-reactive protein) and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (up to 78%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than DNA methylation potentially regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of pro-inflammatory genes regulation that cannot fully be explained by differential DNA methylation.

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Mutual regulation of microRNAs and DNA methylation in human cancers

Cited by 123 publications

References 126 publications

The Effect of NNK, A Tobacco Smoke Carcinogen, on the miRNA and Mismatch DNA Repair Expression Profiles in Lung and Head and Neck Squamous Cancer Cells

The Effect of NNK, A Tobacco Smoke Carcinogen, on the miRNA and Mismatch DNA Repair Expression Profiles in Lung and Head and Neck Squamous Cancer Cells

Identification of Epigenetic Interactions between MicroRNA and DNA Methylation Associated with Polycystic Ovarian Syndrome

Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two European cohort studies

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