scholarly journals Ovarian cancer: epigenetics, drug resistance, and progression

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Weiwei Xie ◽  
Huizhen Sun ◽  
Xiaoduan Li ◽  
Feikai Lin ◽  
Ziliang Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Dna Sequences ◽  
Histone Deacetylase Inhibitors ◽  
Malignant Tumors ◽  
Clinical Investigation ◽  
Cancer Epigenetics ◽  
Novel Approach ◽  
Non Coding Rna ◽  
Epigenetic Processes

AbstractOvarian cancer (OC) is one of the most common malignant tumors in women. OC is associated with the activation of oncogenes, the inactivation of tumor suppressor genes, and the activation of abnormal cell signaling pathways. Moreover, epigenetic processes have been found to play an important role in OC tumorigenesis. Epigenetic processes do not change DNA sequences but regulate gene expression through DNA methylation, histone modification, and non-coding RNA. This review comprehensively considers the importance of epigenetics in OC, with a focus on microRNA and long non-coding RNA. These types of RNA are promising molecular markers and therapeutic targets that may support precision medicine in OC. DNA methylation inhibitors and histone deacetylase inhibitors may be useful for such targeting, with a possible novel approach combining these two therapies. Currently, the clinical application of such epigenetic approaches is limited by multiple obstacles, including the heterogeneity of OC, insufficient sample sizes in reported studies, and non-optimized methods for detecting potential tumor markers. Nonetheless, the application of epigenetic approaches to OC patient diagnosis, treatment, and prognosis is a promising area for future clinical investigation.

scholarly journals Extracting a biologically latent space of lung cancer epigenetics with variational autoencoders

2019 ◽  
Vol 20 (S18) ◽  
Author(s):  
Zhenxing Wang ◽  
Yadong Wang
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Deep Learning ◽  
Malignant Tumors ◽  
Methylation Data ◽  
Cancer Epigenetics ◽  
Latent Space ◽  
Unsupervised Deep Learning ◽  
Latent Representations ◽  
Model Training

Abstract Background Lung cancer is one of the most malignant tumors, causing over 1,000,000 deaths each year worldwide. Deep learning has brought success in many domains in recent years. DNA methylation, an epigenetic factor, is used for model training in many studies. There is an opportunity for deep learning methods to analyze the lung cancer epigenetic data to determine their subtypes for appropriate treatment. Results Here, we employ variational autoencoders (VAEs), an unsupervised deep learning framework, on 450K DNA methylation data of TCGA-LUAD and TCGA-LUSC to learn latent representations of the DNA methylation landscape. We extract a biologically relevant latent space of LUAD and LUSC samples. It is showed that the bivariate classifiers on the further compressed latent features could classify the subtypes accurately. Through clustering of methylation-based latent space features, we demonstrate that the VAEs can capture differential methylation patterns about subtypes of lung cancer. Conclusions VAEs can distinguish the original subtypes from manually mixed methylation data frame with the encoded features of latent space. Further applications about VAEs should focus on fine-grained subtypes identification for precision medicine.

scholarly journals Long non-coding RNA THOR promotes Ovarian Cancer cells progression via STAT3 pathway

2020 ◽  
Author(s):  
Jing Ge ◽  
Tao Han ◽  
Lili Shan ◽  
Jing Na ◽  
Ya Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Malignant Tumors ◽  
Ovarian Cancer Cells ◽  
Self Renewal ◽  
Stat3 Signaling ◽  
Non Coding Rna ◽  
The Impact ◽  
Long Non Coding Rna

Abstract Background Ovarian cancer (OC) is one of the most common malignant tumors in the world. The prognosis of OC remains poor due to the advanced stage and distant metastasis at the time of diagnosis. Recently, a novel lncRNA, THOR (testis-associated highly conserved oncogenic long non-coding RNA), was characterized in human cancers and shown to exhibit an oncogenic role. However, the role of THOR in OC was still unknown.Methods RT-PCR and western blot analysis were used to detect the expression of THOR and p-STAT3. The impact of THOR on OC proliferation, metastasis and self-renew was investigated in vitro and in vivo . The prognostic value of THOR was determined in OC patient cohorts.Results In this study, our results found that THOR was markedly upregulated in human OC tissues and predict the poor prognosis of OC patients. THOR knockdown resulted in significant inhibition of the growth, metastasis and self-renewal of OC cells. Mechanistically, THOR drives OC cell progression via the STAT3 signaling. Moreover, the specific STAT3 inhibitor S3I-201 diminished the discrepancy in the growth, metastatic and self-renewal capacity between THOR-silenced OC cells and control cells, which further confirmed that STAT3 was required in THOR-driven OC cells progression.Conclusion Our findings revealed that THOR could promote OC cells growth, metastasis and self-renew by activating STAT3 signaling and may be a good predictive factor and therapeutic target.

scholarly journals Long non-coding RNA THOR promotes Ovarian Cancer cells progression via IL-6/STAT3 pathway

2020 ◽  
Author(s):  
Jing Ge ◽  
Tao Han ◽  
Lili Shan ◽  
Jing Na ◽  
Ya Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Malignant Tumors ◽  
Ovarian Cancer Cells ◽  
Self Renewal ◽  
Stat3 Signaling ◽  
Non Coding Rna ◽  
The Impact ◽  
Long Non Coding Rna

Abstract Background: Ovarian cancer (OC) is one of the most common malignant tumors in the world. The prognosis of OC remains poor due to the advanced stage and distant metastasis at the time of diagnosis. Recently, a novel lncRNA, THOR (testis-associated highly conserved oncogenic long non-coding RNA), was characterized in human cancers and shown to exhibit an oncogenic role. However, the role of THOR in OC remains unclear. Methods: RT-PCR and western blot analysis were used to detect the expression of THOR, p-STAT3 and IL-6. The impact of THOR on OC proliferation, metastasis and self-renewal was investigated in vitro and in vivo. The prognostic value of THOR was determined in OC patient cohorts. Results: In this study, our results find that THOR is markedly upregulated in human OC tissues and predicts the poor prognosis of OC patients. Functional studies have revealed that knockdown of THOR inhibits the growth, metastasis and self-renewal of OC cells. Mechanistically, THOR drives OC cell progression via the IL-6/STAT3 signaling. Moreover, the specific STAT3 inhibitor S3I-201 or IL-6R inhibitor tocilizumab diminish the discrepancy in the growth, metastatic and self-renewal capacity between THOR-silenced OC cells and control cells, which further confirm that IL-6/STAT3 is required in THOR-driven OC cells progression. Conclusion: Our findings reveal that THOR could promote OC cells growth, metastasis and self-renewal by activating IL-6/STAT3 signaling and may be a good predictive factor and therapeutic target.

scholarly journals The Epigenetic Landscape of Vascular Calcification: An Integrative Perspective

2020 ◽  
Vol 21 (3) ◽  
pp. 980 ◽  
Author(s):  
Yi-Chou Hou ◽  
Chien-Lin Lu ◽  
Tzu-Hang Yuan ◽  
Min-Tser Liao ◽  
Chia-Ter Chao ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone Modification ◽  
Vascular Calcification ◽  
Calcium Deposition ◽  
Non Coding Rna ◽  
Physico Chemical ◽  
Variable Combination ◽  
Epigenetic Signatures ◽  
Epigenetic Processes

Vascular calcification (VC) is an important complication among patients of advanced age, those with chronic kidney disease, and those with diabetes mellitus. The pathophysiology of VC encompasses passive occurrence of physico-chemical calcium deposition, active cellular secretion of osteoid matrix upon exposure to metabolically noxious stimuli, or a variable combination of both processes. Epigenetic alterations have been shown to participate in this complex environment, through mechanisms including DNA methylation, non-coding RNAs, histone modifications, and chromatin changes. Despite such importance, existing reviews fail to provide a comprehensive view of all relevant reports addressing epigenetic processes in VC, and cross-talk between different epigenetic machineries is rarely examined. We conducted a systematic review based on PUBMED and MEDLINE databases up to 30 September 2019, to identify clinical, translational, and experimental reports addressing epigenetic processes in VC; we retrieved 66 original studies, among which 60.6% looked into the pathogenic role of non-coding RNA, followed by DNA methylation (12.1%), histone modification (9.1%), and chromatin changes (4.5%). Nine (13.6%) reports examined the discrepancy of epigenetic signatures between subjects or tissues with and without VC, supporting their applicability as biomarkers. Assisted by bioinformatic analyses blending in each epigenetic component, we discovered prominent interactions between microRNAs, DNA methylation, and histone modification regarding potential influences on VC risk.

scholarly journals Integration of sperm ncRNA-directed DNA methylation and DNA methylation-directed histone retention in epigenetic transgenerational inheritance

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Daniel Beck ◽  
Millissia Ben Maamar ◽  
Michael K. Skinner
Keyword(s):  
Dna Methylation ◽  
Potential Role ◽  
Epigenetic Alterations ◽  
Adult Males ◽  
Transgenerational Inheritance ◽  
Non Coding Rna ◽  
F2 Generation ◽  
Genetic Form ◽  
F1 Generation ◽  
Epigenetic Processes

Abstract Background Environmentally induced epigenetic transgenerational inheritance of pathology and phenotypic variation has been demonstrated in all organisms investigated from plants to humans. This non-genetic form of inheritance is mediated through epigenetic alterations in the sperm and/or egg to subsequent generations. Although the combined regulation of differential DNA methylated regions (DMR), non-coding RNA (ncRNA), and differential histone retention (DHR) have been shown to occur, the integration of these different epigenetic processes remains to be elucidated. The current study was designed to examine the integration of the different epigenetic processes. Results A rat model of transiently exposed F0 generation gestating females to the agricultural fungicide vinclozolin or pesticide DDT (dichloro-diphenyl-trichloroethane) was used to acquire the sperm from adult males in the subsequent F1 generation offspring, F2 generation grand offspring, and F3 generation great-grand offspring. The F1 generation sperm ncRNA had substantial overlap with the F1, F2 and F3 generation DMRs, suggesting a potential role for RNA-directed DNA methylation. The DMRs also had significant overlap with the DHRs, suggesting potential DNA methylation-directed histone retention. In addition, a high percentage of DMRs induced in the F1 generation sperm were maintained in subsequent generations. Conclusions Many of the DMRs, ncRNA, and DHRs were colocalized to the same chromosomal location regions. Observations suggest an integration of DMRs, ncRNA, and DHRs in part involve RNA-directed DNA methylation and DNA methylation-directed histone retention in epigenetic transgenerational inheritance.

scholarly journals Comprehensive Analysis of the Potential Immune-Related Biomarker Transporter Associated With Antigen Processing 1 That Inhibits Metastasis and Invasion of Ovarian Cancer Cells

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaoxue Li ◽  
Shiyu Zeng ◽  
Yiling Ding ◽  
Yanting Nie ◽  
Mengyuan Yang
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Transcription Factors ◽  
Immune Checkpoint ◽  
Poor Prognosis ◽  
Antigen Processing ◽  
Malignant Tumors ◽  
Immunological Methods ◽  
Immune Infiltration ◽  
Checkpoint Genes

Transporter associated with antigen processing 1 (TAP1) is a protein related immune regulation and plays a role in several malignant tumors. However, the effect of TAP1 on immune infiltration, immunotherapy, and metastasis in different cancers has not been reported till date. The cancer genome atlas database, the tumor immune estimation resource database, and the estimation of stromal and immune cells in malignant tumors using expression (ESTIMATE) algorithm were used to determine the correlation between TAP1 expression and the prognosis of a variety of cancers, immune infiltration, immune checkpoint genes, DNA methylation, and neoantigens. Various enrichment analyses were used to study the correlation between TAP1 and key transcription factors using the Kyoto encyclopedia of genes and genomes (KEGG) pathway in ovarian cancer. Immunological methods were used to evaluate the expression of TAP1 protein in ovarian and cervical cancer, and Kaplan–Meier analysis was used to analyze the prognostic value of TAP1. RNA interference (RNAi) was used to verify the effect of TAP1 on ovarian cancer. Compared with normal tissues, cancer tissues showed a significant increase in the expression of TAP1, and TAP1 expression was related to the poor prognosis of cancers such as ovarian cancer. The expression level of TAP1 was correlated with immune checkpoint genes, DNA methylation, tumor mutation burden, microsatellite instability, and neoantigens in various cancers. Our results showed that TAP1 was upregulated in ovarian cancer cell lines and was associated with poor prognosis. Further, we verified the expression of TAP1-related transcription factors (MEF2A and LEF1) and found that TAP1 was closely related to ovarian cancer metastasis in vitro and in vivo. These results indicated that TAP1 could be used as a biomarker for the diagnosis and prognosis of cancer and as a new therapeutic target.

scholarly journals Association of Lsh, a Regulator of DNA Methylation, with Pericentromeric Heterochromatin Is Dependent on Intact Heterochromatin

2003 ◽  
Vol 23 (23) ◽  
pp. 8416-8428 ◽  
Author(s):  
Qingsheng Yan ◽  
Edward Cho ◽  
Stephen Lockett ◽  
Kathrin Muegge
Keyword(s):  
Dna Methylation ◽  
Dna Sequences ◽  
Cellular Localization ◽  
Histone Deacetylase Inhibitors ◽  
Cpg Methylation ◽  
Pericentromeric Heterochromatin ◽  
Prolonged Treatment ◽  
Direct Role ◽  
Heterochromatin Formation ◽  
Heterochromatin Structure

ABSTRACT The eukaryotic genome is packaged into distinct domains of transcriptionally active euchromatin and silent heterochromatin. A hallmark of mammalian heterochromatin is CpG methylation. Lsh, a member of the SNF2 family, is a major regulator of DNA methylation in mice and thus crucial for normal heterochromatin formation. In order to define the molecular function of Lsh, we examined its cellular localization and its association with chromatin. Our studies demonstrate that Lsh is an exclusively nuclear protein, and we define a nuclear localization domain within the N-terminal portion of Lsh. Lsh strongly associates with chromatin and requires the internal and C-terminal regions for this interaction. Lsh accumulates at pericentromeric heterochromatin, suggesting a direct role for Lsh in the methylation of centromeric DNA sequences and the formation of heterochromatin. In search of a signal that is responsible for Lsh recruitment to pericentromeric heterochromatin, we found that histone tail modifications were critical. Prolonged treatment with histone deacetylase inhibitors has been reported to disrupt higher-order heterochromatin organization, and this was accompanied by dissociation of Lsh from pericentromeric heterochromatin. These results are consistent with a model in which Lsh is recruited by intact heterochromatin structure and then assists in maintaining heterochromatin organization by establishing CpG methylation patterns.

scholarly journals Long non-coding RNA Lnc-LALC facilitates colorectal cancer liver metastasis via epigenetically silencing LZTS1

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Chuan Zhang ◽  
Lu Wang ◽  
Chi Jin ◽  
Jiahui Zhou ◽  
Chaofan Peng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Liver Metastasis ◽  
Malignant Tumors ◽  
Methylation Status ◽  
Dna Methyltransferases ◽  
Non Coding Rna ◽  
Long Non Coding Rna

AbstractColorectal cancer (CRC) is one of the most common cancers around the world and endangers human health seriously. Liver metastasis is an important factor affecting the long-term prognosis of CRC and the specific mechanism of CRLM (colorectal cancer with liver metastasis) is not fully understood. LZTS1 has been found dysregulated in many cancers, especially in CRC. Theories suggested that hypermethylation of the promoter regions of LZTS1 was responsible for LZTS1 abnormal expression in multiple malignant tumors. Although the role of LZTS1 in CRC cell proliferation has been reported, its role in CRLM remains unclear. Numerous studies reported Long non-coding RNA (lncRNA) could regulate the gene expression level by regulating gene methylation status in many tumors. However, whether there were lncRNAs could change the methylation status of LZTS1 or not in CRLM was unknown. In this study, we aimed to investigate whether there are lncRNAs can regulate the expression of LZTS1 through affecting DNA methylation in CRLM. We found that upregulated Lnc-LALC in CRC was negatively correlated with LZTS1 expression, and Lnc-LALC could regulate LZTS1 expression in both mRNA and protein level in our study. Functionally, Lnc-LALC enhanced the CRC cells metastasis ability in vitro and vivo through inhibiting the expression of LZTS1. Furthermore, the precise mechanisms exploration showed that lnc-LALC could recruit DNA methyltransferases (DNMTs) to the LZTS1 promoter by combining with Enhancer of zeste homolog 2(EZH2) and then altered the expression of LZTS1 via DNMTs-mediated DNA methylation. Collectively, our data demonstrated the important role of Lnc-LALC/ LZTS1 axis in CRLM development.

DNA methylation in satellite repeats disorders

2019 ◽  
Vol 63 (6) ◽  
pp. 757-771 ◽  
Author(s):  
Claire Francastel ◽  
Frédérique Magdinier
Keyword(s):  
Dna Methylation ◽  
Human Genome ◽  
Repetitive Dna ◽  
Dna Sequences ◽  
Satellite Repeats ◽  
Tremendous Progress ◽  
Genes Encoding ◽  
Dna Elements ◽  
Near Future

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.

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