Promising microRNAs in pre-diagnostic serum associated with lung cancer up to eight years before diagnosis: a HUNT study.

Introduction: Blood biomarkers for early detection of lung cancer (LC) are in demand. There are few studies of the full microRNome in serum of asymptomatic subjects that later develop LC. Here we searched for novel microRNA biomarkers in blood from non-cancer, ever-smokers populations up to eight years before diagnosis.

Serum small RNAs in metastatic colorectal cancer predict response to chemotherapy and characterize high-risk patients.

Metastatic colorectal cancer (mCRC) presents significant challenges in clinical management due to its heterogeneity and variable response to treatment. In this study, we conducted comprehensive small RNA (sRNA) sequencing analyses to identify sRNA biomarkers associated with survival and treatment response in mCRC patients. We measured serum sRNAs before and after chemotherapy treatment in a discovery cohort of 189 mCRC patients.

IL-32 is induced by activation of toll-like receptors in multiple myeloma cells.

Multiple myeloma (MM) is a hematological cancer characterized by accumulation of malignant plasma cells in the bone marrow. The patients are immune suppressed and suffer from recurrent and chronic infections. Interleukin-32 is a non-conventional, pro-inflammatory cytokine expressed in a subgroup of MM patients with a poor prognosis.

Assessment of Two Commercial Comprehensive Gene Panels for Personalized Cancer Treatment.

(1) Background: Analysis of tumor DNA by next-generation sequencing (NGS) plays various roles in the classification and management of cancer. This study aimed to assess the performance of two similar and large, comprehensive gene panels with a focus on clinically relevant variant detection and tumor mutation burden (TMB) assessment; (2) Methods: DNA from 19 diagnostic small cell lung cancer biopsies and an AcroMetrix™ assessment sample with >500 mutations were sequenced using Oncomine™ Comprehensive Assay Plus (OCAP) on the Ion Torrent platform and TruSight Oncology 500 Assay (TSO500) on the Illumina platform; (3) Results: OCAP and TSO500 achieved comparable NGS quality, such as mean read coverage and mean coverage uniformity. A total of 100% of the variants in the diagnostic samples and 80% of the variants in the AcroMetrix™ assessment sample were detected by both panels, and the panels reported highly similar variant allele frequency.

Comprehensive small RNA-sequencing of primary myeloma cells identifies miR-105-5p as a predictor of patient survival.

Background: Small RNAs (sRNAs), a heterogenous group of non-coding RNAs, are emerging as promising molecules for cancer patient risk stratification and as players in tumour pathogenesis. Here, we have studied microRNAs (miRNAs) and other sRNAs in relation to survival and disease severity in multiple myeloma.

Methods: We comprehensively characterised sRNA expression in multiple myeloma patients by performing sRNA-sequencing on myeloma cells isolated from bone marrow aspirates of 86 myeloma patients.

Increased levels of microRNA-320 in blood serum and plasma is associated with imminent and advanced lung cancer.

Lung cancer (LC) incidence is increasing globally and altered levels of microRNAs (miRNAs) in blood may contribute to identification of individuals with LC. We identified miRNAs differentially expressed in peripheral blood at LC diagnosis and evaluated, in pre-diagnostic blood specimens, how long before diagnosis expression changes in such candidate miRNAs could be detected. We identified upregulated candidate miRNAs in plasma specimens from a hospital-based study sample of 128 patients with confirmed LC and 62 individuals with suspected but confirmed negative LC (FalsePos).

Paired miRNA- and messenger RNA-sequencing identifies novel miRNA-mRNA interactions in multiple myeloma.

Multiple myeloma (MM) is an incurable cancer of terminally differentiated plasma cells that proliferate in the bone marrow. miRNAs are promising biomarkers for risk stratification in MM and several miRNAs are shown to have a function in disease pathogenesis. However, to date, surprisingly few miRNA-mRNA interactions have been described for and functionally validated in MM.

Small RNAs are differentially expressed in autoimmune and non-autoimmune diabetes and controls.

Objective: Diabetes is a heterogeneous disease and a precise diagnosis of diabetes subgroups is necessary to initiate proper early treatment and clinical management of the disease. Circulating small RNAs (sRNAs) are potentially diagnostic biomarkers in diseases, including diabetes. Here we aimed to examine whether profiles of circulating sRNAs differed between patients with autoimmune and non-autoimmune diabetes and non-diabetic controls.

Intracellular IL-32 regulates mitochondrial metabolism, proliferation, and differentiation of malignant plasma cells.

Interleukin-32 (IL-32) is a nonclassical cytokine expressed in cancers, inflammatory diseases, and infections. Its expression is regulated by two different oxygen sensing systems; HIF1α and cysteamine dioxygenase (ADO), indicating that IL-32 may be involved in the response to hypoxia. We here demonstrate that endogenously expressed, intracellular IL-32 interacts with components of the mitochondrial respiratory chain and promotes oxidative phosphorylation.

The first mitochondrial 5-methylcytosine map in a non-model teleost (Oreochromis niloticus) reveals extensive strand-specific and non-CpG methylation.

DNA methylation is one of the main epigenetic mechanisms that regulate gene expression in a manner that depends on the genomic context and varies considerably across taxa. This DNA modification was first found in nuclear genomes of eukaryote several decades ago and it has also been described in mitochondrial DNA. It has recently been shown that mitochondrial DNA is extensively methylated in mammals and other vertebrates.

Epigenetic mapping of the somatotropic axis in Nile tilapia reveals differential DNA hydroxymethylation marks associated with growth.

In vertebrates, the somatotropic axis comprising the pituitary gland, liver and muscle plays a major role in myogenesis. Its output in terms of muscle growth is highly affected by nutritional and environmental cues, and thus likely epigenetically regulated. Hydroxymethylation is emerging as a DNA modification that modulates gene expression but a holistic characterization of the hydroxymethylome of the somatotropic axis has not been investigated to date.

Kisspeptin Influences the Reproductive Axis and Circulating Levels of microRNAs in Senegalese Sole.

Kisspeptin regulates puberty and reproduction onset, acting upstream of the brain-pituitary-gonad (HPG) axis. This study aimed to test a kisspeptin-based hormonal therapy on cultured Senegalese sole (G1) breeders, known to have reproductive dysfunctions. A single intramuscular injection of KISS2-10 decapeptide (250 µg/kg) was tested in females and males during the reproductive season, and gonad maturation, sperm motility, plasma levels of gonadotropins (Fsh and Lh) and sex steroids (11-ketotestosterone, testosterone and estradiol), as well as changes in small non-coding RNAs (sncRNAs) in plasma, were investigated.

sMETASeq: Combined Profiling of Microbiota and Host Small RNAs.

Understanding microbial communities' roles in human health and disease requires methods that accurately characterize the microbial composition and their activity and effects within human biological samples. We present sMETASeq (small RNA Metagenomics by Sequencing), a novel method that uses sequencing of small RNAs to jointly measure host small RNA expression and create metagenomic profiles and detect small bacterial RNAs. We evaluated the performance of sMETASeq on a mock bacterial community and demonstrated its use on different human samples, including colon cancer, oral leukoplakia, cervix cancer, and a panel of human biofluids.

Major gene expression changes and epigenetic remodelling in Nile tilapia muscle after just one generation of domestication.

The historically recent domestication of fishes has been essential to meet the protein demands of a growing human population. Selection for traits of interest during domestication is a complex process whose epigenetic basis is poorly understood. Cytosine hydroxymethylation is increasingly recognized as an important DNA modification involved in epigenetic regulation.

Comprehensive transcriptomic analyses of tissue, serum, and serum exosomes from hepatocellular carcinoma patients.

Background: The expression of microRNAs (miRNAs) is a promising prognostic and diagnostic tool in hepatocellular carcinoma (HCC). Here we performed small RNA sequencing (sRNA-seq) of tissue, serum and serum exosomes to investigate changes in miRNA expression between the different sample types and correlated the expression with clinical parameters. We also performed gene expression arrays on tumor and normal tissue.

Uracil-DNA glycosylase UNG1 isoform variant supports class switch recombination and repairs nuclear genomic uracil.

UNG is the major uracil-DNA glycosylase in mammalian cells and is involved in both error-free base excision repair of genomic uracil and mutagenic uracil-processing at the antibody genes. However, the regulation of UNG in these different processes is currently not well understood. The UNG gene encodes two isoforms, UNG1 and UNG2, each possessing unique N-termini that mediate translocation to the mitochondria and the nucleus, respectively.

Small RNA expression from viruses, bacteria and human miRNAs in colon cancer tissue and its association with microsatellite instability and tumor location.

Background: MicroRNAs (miRNA) and other small RNAs are frequently dysregulated in cancer and are promising biomarkers for colon cancer. Here we profile human, virus and bacteria small RNAs in normal and tumor tissue from early stage colon cancer and correlate the expression with clinical parameters.

Methods: Small RNAs from colon cancer tissue and adjacent normal mucosa of 48 patients were sequenced using Illumina high-throughput sequencing.

Identification of metastasis-associated microRNAs in serum from rectal cancer patients.

MicroRNAs (miRNAs) are promising prognostic and diagnostic biomarkers due to their high stability in blood. Here we investigate the expression of miRNAs and other noncoding (nc) RNAs in serum of rectal cancer patients. Serum from 96 rectal cancer patients was profiled using small RNA sequencing and expression of small RNAs was correlated with the clinicopathological characteristics of the patients.

Cell cycle regulation of human DNA repair and chromatin remodeling genes.

Maintenance of a genome requires DNA repair integrated with chromatin remodeling. We have analyzed six transcriptome data sets and one data set on translational regulation of known DNA repair and remodeling genes in synchronized human cells. These data are available through our new database: www.

Transcription profiling during the cell cycle shows that a subset of Polycomb-targeted genes is upregulated during DNA replication.

Genome-wide gene expression analyses of the human somatic cell cycle have indicated that the set of cycling genes differ between primary and cancer cells. By identifying genes that have cell cycle dependent expression in HaCaT human keratinocytes and comparing these with previously identified cell cycle genes, we have identified three distinct groups of cell cycle genes. First, housekeeping genes enriched for known cell cycle functions; second, cell type-specific genes enriched for HaCaT-specific functions; and third, Polycomb-regulated genes.