DNA Methylation in Lung Cancer: Mechanisms and Associations with Histological Subtypes, Molecular Alterations, and Major Epidemiological Factors

Hoang, Phuc H.; Landi, Maria Teresa

doi:10.3390/cancers14040961

Cited by 38 publications

(21 citation statements)

References 192 publications

(243 reference statements)

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“…For example, several PRMT inhibitors are undergoing phase 1/2 clinical trials [30]. Furthermore, certain methylation markers, such as DAL-1, EPHB6, HS3ST2, TMEM88 and MGMT, specifically associated with lung cancer progression and metastasis, were found to have increased methylation levels [31]. Also, previous research revealed that methylation of the BRCA1 promoter in peripheral blood DNA was linked to a 3.5-fold increased risk (95% CI, 1.4-10.5) of developing breast cancer before the age of 40 [32,33].…”

Section: Discussionmentioning

confidence: 99%

DNA and protein methyltransferases inhibition by adenosine dialdehyde reduces the proliferation and migration of breast and lung cancer cells by downregulating autophagy

Ghemrawi,

Al Qassem,

Ramadan

et al. 2023

PLoS ONE

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Protein and DNA methylation is involved in various biological functions such as signal transmission, DNA repair, and gene expression. Abnormal regulation of methyltransferases has been linked to multiple types of cancer, but its link to autophagy and carcinogenesis in breast and lung cancer is not fully understood. We utilized UALCAN, a web tool, to investigate breast and lung cancer database from The Cancer Genome Atlas. We found that 17 methyltransferases are upregulated in breast and/or lung cancer. We investigated the effect of methylation inhibition on two breast cancer cell lines (MDA-MB-231 and MCF-7) and two lung cancer cell lines (H292 and A549) by treating them with the indirect methyltransferase inhibitor adenosine dialdehyde (AdOx). We found that the migration ability of all cell lines was decreased, and the growth rate of MDA-MB-231, MCF-7 and H292 was also decreased after AdOx treatment. These results were correlated with an inhibition of the autophagy in MDA-MB-231, MCF-7 and H292 cell lines, since AdOx treatment induced a decreased expression of ATG7, a reduced ratio LC3-II/LC3-I and an increased p62 level. These findings suggest that inhibiting cells’ methylation ability could be a potential target for breast and lung cancer treatment.

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Section: Discussionmentioning

confidence: 99%

DNA and protein methyltransferases inhibition by adenosine dialdehyde reduces the proliferation and migration of breast and lung cancer cells by downregulating autophagy

Ghemrawi,

Al Qassem,

Ramadan

et al. 2023

PLoS ONE

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“…Differences in methylation patterns have been observed in the subtypes of lung cancer, mutation status of cancer-driven genes, and various epidemiological factors ( 22 ). Therefore, the identification of methylation sites of cancer-specific genes may be helpful to molecular classification and disease stratification ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis based on DNA methylation data identified in lung adenocarcinoma subgroups with different immune characteristics and clinical outcomes

Yu¹,

Huang²,

Lin³

et al. 2023

J Thorac Dis

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Background DNA methylation can be used to predict clinical outcomes and improve the classification of tumors. The present study aimed to develop a new lung adenocarcinoma (LUAD) classification system according to the immune cell gene-related methylation sites and to reveal the survival outcomes, clinical characteristics, immune cell infiltration, stem cell characteristics, and genomic variations of each molecular subgroup. Methods The DNA methylation sites of LUAD samples collected from The Cancer Genome Atlas (TCGA) database were analyzed, and the prognosis-related differential methylation sites (DMS) were screened. Consistent clustering of the samples was conducted using ConsensusClusterPlus, and the classification results were verified by principal component analysis (PCA). The survival and clinical results, immune cell infiltration, stemness, DNA mutation, and copy number variation (CNV) of each molecular subgroup were analyzed. Results A total of 40 DMS were obtained by difference and univariate COX analyses, and the TCGA LUAD samples were divided into three subgroups: cluster 1 (C1), cluster 2 (C2), and cluster 3 (C3). Among these subgroups, the overall survival (OS) of C3 was significantly higher than that of C1 and C2. Compared with C1 and C3, C2 had the lowest innate immune cell and adaptive immune cell infiltration scores; the lowest stromal score, immune score, and iconic immune checkpoint expression; and the highest expression of messenger RNA (mRNA) expression-based stemness indices (mRNAsi), DNA methylation-based stemness index (mDNAsi), and tumor mutational burden (TMB). Conclusions In this study, we proposed a LUAD typing system based on DMS, which was closely related to the survival, clinical features, immune characteristics, and genomic variations of LUAD, and may contribute to the development of personalized therapy for new specific subtypes.

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“…As shown in the study by Ai et al, triptolide induces the expression of endogenous miR-15a and inhibits the Hippo-yes-associated protein (Hippo-YAP)/TAZ pathway, leading to the cytotoxicity, senescence and apoptosis of ovarian GCs ( Ai et al, 2018 ). Additionally, epigenetic therapy is a promising approach for the treatment of cancers ( Matthews et al, 2021 ; Xu et al, 2021 ; Brown et al, 2022 ; Hoang and Landi 2022 ). Since DNA methylation plays an important role in the formation of primordial germ cells, epigenetic therapy, e.g., DNMT inhibitor-based (such as decitabine) therapies, may hamper oocyte differentiation and development and thus induce POI ( Yang et al, 2019 ).…”

Section: Epigenetic Mechanisms Regulating the Occurrence And Developm...mentioning

confidence: 99%

Epigenetic regulation in premature ovarian failure: A literature review

Wang

Sun²,

Yang

et al. 2023

Front. Physiol.

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Premature ovarian failure (POF), or premature ovarian insufficiency (POI), is a multifactorial and heterogeneous disease characterized by amenorrhea, decreased estrogen levels and increased female gonadotropin levels. The incidence of POF is increasing annually, and POF has become one of the main causes of infertility in women of childbearing age. The etiology and pathogenesis of POF are complex and have not yet been clearly elucidated. In addition to genetic factors, an increasing number of studies have revealed that epigenetic changes play an important role in the occurrence and development of POF. However, we found that very few papers have summarized epigenetic variations in POF, and a systematic analysis of this topic is therefore necessary. In this article, by reviewing and analyzing the most relevant literature in this research field, we expound on the relationship between DNA methylation, histone modification and non-coding RNA expression and the development of POF. We also analyzed how environmental factors affect POF through epigenetic modulation. Additionally, we discuss potential epigenetic biomarkers and epigenetic treatment targets for POF. We anticipate that our paper may provide new therapeutic clues for improving ovarian function and maintaining fertility in POF patients.

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DNA Methylation in Lung Cancer: Mechanisms and Associations with Histological Subtypes, Molecular Alterations, and Major Epidemiological Factors

Cited by 38 publications

References 192 publications

DNA and protein methyltransferases inhibition by adenosine dialdehyde reduces the proliferation and migration of breast and lung cancer cells by downregulating autophagy

DNA and protein methyltransferases inhibition by adenosine dialdehyde reduces the proliferation and migration of breast and lung cancer cells by downregulating autophagy

Bioinformatics analysis based on DNA methylation data identified in lung adenocarcinoma subgroups with different immune characteristics and clinical outcomes

Epigenetic regulation in premature ovarian failure: A literature review

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