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At least 1,423 records · Page 79Linked to original sources
PubMed2002

Gene silencing in mammals by small interfering RNAs.

Among the 3 billion base pairs of the human genome, there are approximately 30,000-40,000 protein-coding genes, but the function of at least half of them remains unknown. A new tool - short interfering RNAs (siRNAs) - has now been developed for systematically deciphering the functions and interactions of these thousands of genes. siRNAs are an intermediate of RNA interference, the process by which double-stranded RNA silences homologous genes. Although the use of siRNAs to silence genes in vertebrate cells was only reported a year ago, the emerging literature indicates that most vertebrate genes can be studied with this technology.

Animals↗
PubMed2004

Molecular mechanisms of translational control.

Translational control is widely used to regulate gene expression. This mode of regulation is especially relevant in situations where transcription is silent or when local control over protein accumulation is required. Although many examples of translational regulation have been described, only a few are beginning to be mechanistically understood. Instead of providing a comprehensive account of the examples that are known at present, we discuss instructive cases that serve as paradigms for different modes of translational control.

Animals↗
PubMed2003

The news and you.

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Alternative Splicing↗
PubMed2004

RISCy business.

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Animals↗
PubMed2004

RNase III enzymes and the initiation of gene silencing.

Our understanding of RNA interference has been enhanced by new data concerning RNase III molecules. The role of Dicer has previously been established in RNAi as the originator of 22-mers characteristic of silencing phenomena. Recently, a related RNAse III enzyme, Drosha, has surfaced as another component of the RNAi pathway. In addition to biochemistry, protein structures have proven to be helpful in deciphering the enzymology of RNase III molecules.

Gene Silencing↗
PubMed2026

Single-cell multiomics reveals exosome-mediated reprogramming and clonotypic remodeling of T cells in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive and immunogenic subtype lacking targeted therapies. While tumor-derived exosomes are known to modulate immune function, their direct impact on human T cell plasticity and antigen specificity remains poorly defined. Here, we conducted a comprehensive single-cell multiomic analysis of primary human T cells exposed to exosomes derived from 17 genomically diverse TNBC cell lines and 35 patient samples. Integrating single-cell RNA-seq, V(D)J sequencing, non-coding RNA profiling, bulk and single-cell cytokine analyses, we uncovered conserved and subtype-specific immunomodulatory programs induced by TNBC exosomes. Exosome-treated T cells displayed skewing toward regulatory and dysfunctional phenotypes, including Th17-like, Treg, and PD-1⁺/PD-L1⁺ Tfh cells. Functional profiling revealed suppression of early activation markers and cytokine responses, alongside selective preservation of cytotoxic features in γδ T and NKT subsets. Transcriptomic and miRNA network analyses demonstrated widespread downregulation of immune effector genes (e.g., HBEGF and TNFSF9) mediated by exosome-delivered regulatory miRNAs (has-miR-98-5p). Notably, exosome-stimulated T cells displayed distinct clonotypic expansions, characterized by the emergence of five tumor-specific γδ TCR clonotypes and 30 unique αβ TCR CDR3 sequences that were absent in mock-treated controls, underscoring the role of exosomes in shaping TCR repertoire dynamics.

Humans↗
PubMed2025

Expression regulation network in papillae of sea cucumbers: Whole-transcriptome and DNA methylation datasets.

To elucidate the expression regulation network of papilla size of sea cucumbers (Apostichopus japonicus), the whole-transcriptome and DNA methylome datasets of different sizes of papillae in sea cucumbers were generated. Average clean bases of whole-transcriptome (16.35 G) and DNA methylome (28.92 G) were obtained using RNA sequencing and whole-genome bisulfite sequencing techniques. A total of 3,188 ceRNA networks were also identified including 3,081 long non-coding RNAs (lncRNA)/microRNAs (miRNA)/mRNA networks and 107 circular RNA (circRNA)/miRNA/mRNA networks. Methylome data indicate that there were 3,307 and 3,776 differentially methylated regions (DMRs) with high-level methylation as well as 3,125 and 3,016 DMRs with low-level methylation in big papillae compared to small papillae. The identified DMRs were mainly distributed in introns, promotors, or exons. The whole-transcriptome and DNA methylome datasets generated from this study not only established a robust theoretical foundation (especially from the epigenetic aspect) for elucidating expression regulation network determining papilla size in sea cucumbers but also can be a valuable resource of biomarker mining for papilla appearance-based selective breeding in sea cucumbers.

DNA Methylation↗
PubMed2025

Short-term diet intervention comprising of olive oil, vitamin D, and omega-3 fatty acids alters the small non-coding RNA (sncRNA) landscape of human sperm.

Offspring health outcomes are often linked with epigenetic alterations triggered by maternal nutrition and intrauterine environment. Strong experimental data also link paternal preconception nutrition with pathophysiology in the offspring, but the mechanism(s) routing effects of paternal exposures remain elusive. Animal experimental models have highlighted small non-coding RNAs (sncRNAs) as potential regulators of paternal effects. Here, we characterised the baseline sncRNA landscape of human sperm and the effect of a 6-week dietary intervention on their expression profile. This study involves sncRNAseq profiling, that was performed on a subset (n = 17) of the participants enrolled in the PREPARE trial: 9 from the control group and 8 from the intervention group. 5'tRFs, miRNAs and piRNAs were the most abundant sncRNA subtypes identified; their expression was associated with age, BMI, and sperm quality. Nutritional intervention with olive oil, vitamin D and omega-3 fatty acids altered expression of 3 tRFs, 15 miRNAs and 112 piRNAs, targeting genes involved in fatty acid metabolism and transposable elements in the sperm genome. PREPARE Trial registration number: ISRCTN50956936, Trial registration date: 10/02/2014.

Humans↗
PubMed2026

Semaglutide treatment in MOSH is associated with altered DNA methylation patterns of genes related to glycolipid metabolism.

Male obesity-associated secondary hypogonadism(MOSH) is a common disease among severely obese male patients. Although surgical interventions have demonstrated clinical benefits, a subset of patients continue to experience MOSH following surgery. Therefore, this study aims to investigate epigenetic changes associated with the use of the weight-loss drug Semaglutide in MOSH, focusing on DNA methylation and miRNA expression. In this exploratory study, samples were classified into three groups: a control group (n = 2), a MOSH group (n = 7), and a follow-up group (n = 4). DNA methylation analysis was performed on all samples, while miRNA sequencing was conducted on a subset of the samples: 2 from the control group, 7 from the MOSH group, and 2 from the follow-up group. Differentially expressed miRNAs (DEMs) were analyzed through the R package "limma", and the methylation level of CpG sites was analyzed based on the methylation β value, obtaining differentially methylated genes (DMGs). The functional enrichment analysis of miRNA target genes and methylation change genes was conducted using the R package "clusterProfiler". Finally, the regulatory networks of miRNA and methylation genes as well as the protein-protein interaction (PPI) network were analyzed. A total of 6 DEMs were screened out. The target genes of these DEMs were mainly enriched in pathways such as ATP binding, phosphorylation, cell adhesion, and Glycosphingolipid biosynthesis. Eighty DMGs were identified, and the largest number of DMGs were found in the X chromosome. In the regulatory network of DMGs and DEMs, hsa-miR-423-5p regulates most of these DMGs. Moreover, the PPI network shows that DPP6, DPP10, CACNA1C, and CNTNAP2 are the proteins with the strongest connectivity. Notably, differential CpG methylation changes were observed on chromosome 7, indicating a potential region of epigenetic alteration in MOSH; however, the biological and functional relevance of these changes remains unclear. Collectively, these findings suggest that Semaglutide treatment in MOSH may be associated with concurrent alterations in DNA methylation and miRNA expression, implicating genes related to energy and glycolipid metabolism, including DPP6, DPP10, CACNA1C, and CNTNAP2. These results are exploratory and hypothesis-generating, providing preliminary observations to inform future validation studies.

Semaglutide↗
PubMed2005

Silencing of endogenous IGFBP-5 by micro RNA interference affects proliferation, apoptosis and differentiation of neuroblastoma cells.

Signal transduction through the IGF axis is implicated in proliferation, differentiation and survival during development and adult life. The IGF axis includes the IGF binding proteins (IGFBPs) that bind IGFs with high affinity and modulate their activity. In neuroblastoma (NB), a malignant childhood tumor, we found that IGFBP-5 is frequently expressed. Since NB is an IGF2-sensitive tumor, we investigated the relevance and the function of endogenous IGFBP-5 in LAN-5 and in SY5Y(N) cell lines transfected with micro and small interfering RNAs directed to IGFBP-5 mRNA. Cells in which IGFBP-5 expression was suppressed were growth-inhibited and more prone to apoptosis than the parental cell line and controls. Apoptosis was further enhanced by X-ray irradiation. The ability of these cells to undergo neuronal differentiation was impaired after IGFBP-5 inhibition but the effect was reversed by exposure to recombinant IGFBP-5. Together, these data demonstrate the importance of IGFBP-5 for NB cell functions and suggest that IGFBP-5 might serve as a novel therapeutic target in NB.

Apoptosis↗
PubMed2006

Mutation screening of brain-expressed X-chromosomal miRNA genes in 464 patients with nonsyndromic X-linked mental retardation.

MiRNAs are small noncoding RNAs that control the expression of target genes at the post-transcriptional level and have been reported to modulate various biological processes. Their function as regulatory factors in gene expression renders them attractive candidates for harbouring genetic variants with subtle effects on IQ. In an attempt to investigate the potential role of miRNAs in the aetiology of X-linked mental retardation, we have examined all 13 known, brain-expressed X-chromosomal miRNAs in a cohort of 464 patients with non-syndromic X-linked MR and found four nucleotide changes in three different pre-miRNA hairpins. All the observed changes appear to be functionally neutral which, taken together with the rarity of detected nucleotide changes in miRNA genes, may reflect strong selection and thus underline the functional importance of miRNAs.

Base Sequence↗