The Impact of Childhood Mental Health and Substance Use on Methylation Aging Into Adulthood.

Objective: To test whether childhood mental health symptoms, substance use, and early adversity accelerate the rate of DNA methylation (DNAm) aging from adolescence to adulthood.

Method: DNAm was assayed from blood samples in 381 participants in both adolescence (mean [SD] age = 13.9 [1.

Development and validation of a tumor immune cell infiltration-related gene signature for recurrence prediction by weighted gene co-expression network analysis in prostate cancer.

Prostate cancer (PCa) is the second most common malignancy in men. Despite multidisciplinary treatments, patients with PCa continue to experience poor prognoses and high rates of tumor recurrence. Recent studies have shown that tumor-infiltrating immune cells (TIICs) are associated with PCa tumorigenesis.

An innovative pyroptosis-related long-noncoding-RNA signature predicts the prognosis of gastric cancer affecting immune cell infiltration landscape.

Gastric cancer (GC) is a worldwide popular malignant tumor. However, the survival rate of advanced GC remains low. Pyroptosis and long non-coding RNAs (lncRNAs) are important in cancer progression.

A Prognostic Survival Model of Pancreatic Adenocarcinoma Based on Metabolism-Related Gene Expression.

Accurately predicting the survival prospects of patients suffering from pancreatic adenocarcinoma (PAAD) is challenging. In this study, we analyzed RNA matrices of 182 subjects with PAAD based on public datasets obtained from The Cancer Genome Atlas (TCGA) as training datasets and those of 63 subjects obtained from the Gene Expression Omnibus (GEO) database as the validation dataset. Genes regulating the metabolism of PAAD cells correlated with survival were identified.

Genetic Alterations in Papillary Thyroid Carcinoma With Hashimotos Thyroiditis： , an Indolent Maintainer of Papillary Thyroid Carcinoma.

Hashimoto's thyroiditis (TH) is a risk factor for the occurrence of papillary thyroid carcinoma (PTC), which is considered to be the most common type of thyroid cancer. In recent years, the prevalence of PTC with TH has been increasing, but little is known about the genetic alteration in PTC with TH. This study analyzed the mutation spectrum and mutation signature of somatic single nucleotide variants (SNV) for 10 non-tumor and tumor pair tissues of PTC with TH using whole-exome sequencing.

An Early-Onset Advanced Rectal Cancer Patient With Increased KRAS Gene Copy Number Showed A Primary Resistance to Cetuximab in Combination With Chemotherapy: A Case Report.

Mutations in (codon 12/13), , and amplification of and account for 70-80% of anti-epidermal growth factor receptor (EGFR) monoclonal antibody primary resistance. However, the list of anti-EGFR monoclonal antibody primary resistance biomarkers is still incomplete. Herein, we report a case of wild-type RAS/BRAF metastatic colorectal cancer (CRC) with resistance to anti-EGFR monoclonal antibody and chemotherapy.

Prognostic role and clinicopathological features of SMAD4 gene mutation in colorectal cancer: a systematic review and meta-analysis.

Background: Approximately 5.0-24.2% of colorectal cancers (CRCs) have inactivating mutations in SMAD4, making it one of the frequently mutated genes in CRC.

CD36 promotes the epithelial-mesenchymal transition and metastasis in cervical cancer by interacting with TGF-β.

Background: Accumulating evidence indicates that CD36 initiates metastasis and correlates with an unfavorable prognosis in cancers. However, there are few reports regarding the roles of CD36 in initiation and metastasis of cervical cancer.

Methods: Using immunohistochemistry, we analyzed 133 cervical cancer samples for CD36 protein expression levels, and then investigated the correlation between changes in its expression and clinicopathologic parameters.

A Whole Methylome Study of Ethanol Exposure in Brain and Blood: An Exploration of the Utility of Peripheral Blood as Proxy Tissue for Brain in Alcohol Methylation Studies.

Background: Recent reviews have highlighted the potential use of blood-based methylation biomarkers as diagnostic and prognostic tools of current and future alcohol use and addiction. Due to the substantial overlap that often exists between methylation patterns across different tissues, including blood and brain, blood-based methylation may track methylation changes in brain; however, little work has explored the overlap in alcohol-related methylation in these tissues.

Methods: To study the effects of alcohol on the brain methylome and identify possible biomarkers of these changes in blood, we performed a methylome-wide association study in brain and blood from 40 male DBA/2J mice that received either an acute ethanol (EtOH) or saline intraperitoneal injection.

Building a schizophrenia genetic network: transcription factor 4 regulates genes involved in neuronal development and schizophrenia risk.

The transcription factor 4 (TCF4) locus is a robust association finding with schizophrenia (SCZ), but little is known about the genes regulated by the encoded transcription factor. Therefore, we conducted chromatin immunoprecipitation sequencing (ChIP-seq) of TCF4 in neural-derived (SH-SY5Y) cells to identify genome-wide TCF4 binding sites, followed by data integration with SCZ association findings. We identified 11 322 TCF4 binding sites overlapping in two ChIP-seq experiments.

Methyl-CpG-Binding Domain Sequencing: MBD-seq.

Detailed biological knowledge about the potential importance of the methylome is typically lacking for common diseases. Therefore, methylome-wide association studies (MWAS) are critical to detect disease relevant methylation sites. Methyl-CpG-binding domain sequencing (MBD-seq) offers potential advantages compared to antibody-based enrichment, but performance depends critically on using an optimal protocol.

Deep Sequencing of 71 Candidate Genes to Characterize Variation Associated with Alcohol Dependence.

Background: Previous genomewide association studies (GWASs) have identified a number of putative risk loci for alcohol dependence (AD). However, only a few loci have replicated and these replicated variants only explain a small proportion of AD risk. Using an innovative approach, the goal of this study was to generate hypotheses about potentially causal variants for AD that can be explored further through functional studies.

AKAP-9 promotes colorectal cancer development by regulating Cdc42 interacting protein 4.

Our previous studies have shown that PRKA kinase anchor protein 9 (AKAP-9) is involved in colorectal cancer (CRC) cell proliferation and migration in vitro. However, whether or not AKAP-9 is important for CRC development or metastasis in vivo remains unknown. In the present study, we found that AKAP-9 expression was significantly higher in human colorectal cancer tissues than the paired normal tissues.

Long non-coding RNA MALAT1 increases AKAP-9 expression by promoting SRPK1-catalyzed SRSF1 phosphorylation in colorectal cancer cells.

Our earlier findings indicate that the long non-coding RNA MALAT1 promotes colorectal cancer (CRC) cell proliferation, invasion and metastasis in vitro and in vivo by increasing expression of AKAP-9. In the present study, we investigated the molecular mechanism by which MALAT1 enhances AKAP9 expression in CRC SW480 cells. We found that MALAT1 interacts with both SRPK1 and SRSF1.

Deep Sequencing of Three Loci Implicated in Large-Scale Genome-Wide Association Study Smoking Meta-Analyses.

Introduction: Genome-wide association study meta-analyses have robustly implicated three loci that affect susceptibility for smoking: CHRNA5\CHRNA3\CHRNB4, CHRNB3\CHRNA6 and EGLN2\CYP2A6. Functional follow-up studies of these loci are needed to provide insight into biological mechanisms. However, these efforts have been hampered by a lack of knowledge about the specific causal variant(s) involved.

Evaluation of Methyl-Binding Domain Based Enrichment Approaches Revisited.

Methyl-binding domain (MBD) enrichment followed by deep sequencing (MBD-seq), is a robust and cost efficient approach for methylome-wide association studies (MWAS). MBD-seq has been demonstrated to be capable of identifying differentially methylated regions, detecting previously reported robust associations and producing findings that replicate with other technologies such as targeted pyrosequencing of bisulfite converted DNA. There are several kits commercially available that can be used for MBD enrichment.

Combined Whole Methylome and Genomewide Association Study Implicates CNTN4 in Alcohol Use.

Background: Methylome-wide association (MWAS) studies present a new way to advance the search for biological correlates for alcohol use. A challenge with methylation studies of alcohol involves the causal direction of significant methylation-alcohol associations. One way to address this issue is to combine MWAS data with genomewide association study (GWAS) data.

MALAT1 promotes colorectal cancer cell proliferation/migration/invasion via PRKA kinase anchor protein 9.

Our previous studies have shown that the 3' end of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is involved in colorectal cancer (CRC) cell proliferation and migration/invasion in vitro. The role and mechanism of MALAT1 in CRC metastasis in vivo, however, remain largely unknown. In the present study, we found that MALAT1 was up-regulated in human primary CRC tissues with lymph node metastasis.

Refinement of schizophrenia GWAS loci using methylome-wide association data.

Recent genome-wide association studies (GWAS) have made substantial progress in identifying disease loci. The next logical step is to design functional experiments to identify disease mechanisms. This step, however, is often hampered by the large size of loci identified in GWAS that is caused by linkage disequilibrium between SNPs.

Humanizing mouse folate metabolism: conversion of the dual-promoter mouse folylpolyglutamate synthetase gene to the human single-promoter structure.

The mouse is extensively used to model human folate metabolism and therapeutic outcomes with antifolates. However, the folylpoly-γ-glutamate synthetase (fpgs) gene, whose product determines folate/antifolate intracellular retention and antifolate antitumor activity, displays a pronounced species difference. The human gene uses only a single promoter, whereas the mouse uses two: P2, akin to the human promoter, at low levels in most tissues; and P1, an upstream promoter used extensively in liver and kidney.

Methylome-wide association study of schizophrenia: identifying blood biomarker signatures of environmental insults.

Importance: Epigenetic studies present unique opportunities to advance schizophrenia research because they can potentially account for many of its clinical features and suggest novel strategies to improve disease management.

Objective: To identify schizophrenia DNA methylation biomarkers in blood.

Design, Setting, And Participants: The sample consisted of 759 schizophrenia cases and 738 controls (N = 1497) collected in Sweden.

[Expression of long noncoding RNA MALAT1 gene in human nasopharyngeal carcinoma cell lines and its biological significance].

Objective: To explore the expression of MALAT 1 in nasopharyngeal carcinoma (NPC) and its biological function.

Method: Real-time PCR was used to detect the expression of MALAT1 in 5-8F, C666-1, CNE-1, CNE-2, HONE-1, 6-10B and NP69 cell lines. CNE-1 cells engineered with MALAT1 RNA interference (RNAi) and RNA activation (RNAa) techniques were examined for changes in cell proliferation, invasion and metastasis using CCK8 assay, colony formation assay, Transwell in vitro invasion assay and wound-healing assay ability.

A mouse gene that coordinates epigenetic controls and transcriptional interference to achieve tissue-specific expression.

The mouse fpgs gene uses two distantly placed promoters to produce functionally distinct isozymes in a tissue-specific pattern. We queried how the P1 and P2 promoters were differentially controlled. DNA methylation of the CpG-sparse P1 promoter occurred only in tissues not initiating transcription at this site.