The p63 transcription factor, a p53 family protein, regulates genes involved in various cellular processes, including cell growth and differentiation. We previously showed that RNA-binding motif ...protein (Rbm38) is a p63 target and, in turn, regulates p63α mRNA stability by binding to the AU/U-rich element in its 3′UTR. Interestingly, Rbm38 can be phosphorylated at serine 195, altering its ability to regulate mRNA translation. However, whether the Ser-195 phosphorylation affects Rbm38’s ability to destabilize p63 mRNA remains unclear. Here, using MCF7 and HaCaT cells, we showed that ectopic expression of phosphomimetic Rbm38-S195D increases, whereas WT Rbm38 and nonphosphorylatable Rbm38-S195A decrease p63α protein and transcript levels. We also found that upon activation of glycogen synthase kinase 3β (GSK3β), phosphorylation of Rbm38 at Ser-195 is increased, enhancing p63α expression in an Rbm38-dependent manner. To confirm this, we generated mouse embryo fibroblasts (MEFs) in which Ser-193 in mouse Rbm38 (equivalent to Ser-195 in human Rbm38) was substituted with aspartic acid (Rbm38S193D/S193D) or alanine (Rbm38S193A/S193A). We observed that the p63 transcript level was increased in Rbm38S193D/S193D MEFs, but decreased in Rbm38S193A/S193A MEFs. Mechanistically, we found that WT Rbm38, but not Rbm38-S195D, is required for p63 mRNA degradation mediated by microRNA 203 (miR203). Furthermore, we noted that Argonaute 2 (Ago2), a key regulator in microRNA-mediated mRNA decay, associates with WT Rbm38, and this association was reduced by Ser-195 phosphorylation. Together, our results reveal a critical mechanism by which Ser-195 phosphorylation in Rbm38 increases p63 expression by attenuating the association of Rbm38 with the Ago2–miR203 complex.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Emerging shreds of evidence suggest that tumor-associated macrophages (TAMs) modulate various hallmarks of cancer during tumor progression. Tumor microenvironment (TME) prime TAMs to execute ...important roles in cancer development and progression, including angiogenesis, matrix metalloproteinases (MMPs) secretion, and extracellular matrix (ECM) disruption. MicroRNAs (miRNAs) are critical epigenetic regulators, which modulate various functions in diverse types of cells, including macrophages associated with TME. In this review article, we provide an update on miRNAs regulating differentiation, maturation, activation, polarization, and recruitment of macrophages in the TME. Furthermore, extracellular miRNAs are secreted from cancerous cells, which control macrophages phenotypic plasticity to support tumor growth. In return, TAMs also secrete various miRNAs that regulate tumor growth. Herein, we also describe the recent updates on the molecular connection between tumor cells and macrophages. A better understanding of the interaction between miRNAs and TAMs will provide new pharmacological targets to combat cancer.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In the last decade, many diverse RNAi (RNA interference) pathways have been discovered that mediate gene silencing at epigenetic, transcriptional and post-transcriptional levels. The diversity of ...RNAi pathways is inherently linked to the evolution of Ago (Argonaute) proteins, the central protein component of RISCs (RNA-induced silencing complexes). An increasing number of diverse Agos have been identified in different species. The functions of most of these proteins are not yet known, but they are generally assumed to play roles in development, genome stability and/or protection against viruses. Recent research in the nematode Caenorhabditis elegans has expanded the breadth of RNAi functions to include transgenerational epigenetic memory and, possibly, environmental sensing. These functions are inherently linked to the production of secondary siRNAs (small interfering RNAs) that bind to members of a clade of WAGOs (worm-specific Agos). In the present article, we review briefly what is known about the evolution and function of Ago proteins in eukaryotes, including the expansion of WAGOs in nematodes. We postulate that the rapid evolution of WAGOs enables the exceptional functional plasticity of nematodes, including their capacity for parasitism.
Over the last decade, circulating microRNAs have received attention as diagnostic and prognostic biomarkers. In particular, microRNA122 has been demonstrated to be an early and more sensitive ...indicator of drug-induced liver injury than the widely used biomarkers such as alanine aminotransferase and aspartate aminotransferase. Recently, microRNA122 has been used in vitro to assess the cellular toxicity of new drugs and as a biomarker for the development of a rapid test for drug overdose/liver damage. In this proof-of-concept study, we report a PCR-free and label-free detection method that has a limit of detection (3 standard deviations) of 15 fmoles of microRNA122, by integrating a dynamic chemical approach for “Single Nucleobase Labelling” with a bead-based platform (Luminex®) thereby, in principle, demonstrating the exciting prospect of rapid and accurate profiling of any microRNAs related to diseases and toxicology.
Display omitted
•Direct detection of native microRNAs via Single Nucleotide Labelling.•Detection of native nucleic acids with single base resolution.•One hour assay for direct detection of miRNA with a LoD of 15 fmole.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Liquid biopsies are a novel technique to assess for either circulating tumor cells (CTC) or circulating tumor DNA (ctDNA and microRNA (miRNA)) in peripheral blood samples of cancer patients. The ...diagnostic role of liquid biopsy in oncology has expanded in recent years, particularly in lung, colorectal and breast cancer. In thyroid cancer, the role of liquid biopsy in either diagnosis or prognosis is beginning to translate from the lab to the clinic. In this review, we describe the evolution of liquid biopsies in detecting CTC, ctDNA and miRNA in thyroid cancer patients, together with its limitations and future directions in clinical practice.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Neoadjuvant chemotherapy (NAC) is an effective therapeutic regimen for patients with breast cancer. However, some individuals cannot benefit from NAC because of drug resistance. To date, valid ...strategies about enhancing sensitivity of breast cancer to NAC are still scarce. miRNAs have been reported to proverbially be involved in the onset and development of malignancies including drug resistance.
GSE73736 was downloaded from the GEO database. Student's
-test was conducted to acquire differentially expressed-miRNAs (DE-miRNAs). Potential target genes of DE-miRNAs were predicted by miRTarBase. Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses for these target genes were performed by database for annotation, visualization, and integrated discovery. Protein-protein interaction network was constructed by STRING database and visualized through Cytoscape software. The hub target gene-miRNA network was also established by Cytoscape software. Next, the expression of potential functional miRNAs in breast cancer cell lines and tissues was determined. Finally, the roles of miR-3617-3p, miR-3136-3p, and miR-520b in modulating breast cancer chemoresistance were further examined.
A total of 123 DE-miRNAs were identified, including 60 upregulated miRNAs and 63 downregulated miRNAs in the chemoresistant breast cancer group when compared with the chemosensitive group. Six hundred and seventeen and 1,146 potential target genes for the top 10 most upregulated and downregulated miRNAs were predicted, respectively. Enrichment analyses revealed that these target genes were enriched in some cancer-associated or chemo-resistance-associated pathways, such as MAPK signaling pathway, wnt signaling pathway, and p53 signaling pathway.
and
were identified as hub genes in the protein-protein interaction network. The top 25 hub genes were potentially regulated by 16 DE-miRNAs, among which miR-3617-3p and miR-3136-3p were commonly upregulated, whereas miR-520b was downregulated in two chemoresistant breast cancer cells compared with chemosensitive cell. By analyzing TCGA data, we found that expression of miR-3136-3p and miR-520b was increased and decreased in breast cancer tissues, respectively. Moreover, functional experiments demonstrated that miR-3136-3p and miR-3617-3p could reduce chemosensitivity of breast cancer, whereas miR-520b could reverse chemoresistance.
The present study, based on bioinformatics analysis and experimental validation, brings to light novel mechanisms of breast cancer NAC resistance.
Many microRNAs (miRNAs) are clustered on chromosomes and co-transcribed as polycistronic transcripts. Here, an integrated evolutionary analysis of human miRNA gene clusters and families was ...performed. Generally, miRNA gene clusters include 2–8 members, but some larger clusters have been found to have more members (over 40 miRNAs). 62.22% of them have been shown to be involved in homologous miRNA genes, including multicopy pre-miRNAs and sense/antisense homologous miRNAs. Multicopy pre-miRNAs can enrich the distribution and relationship between miRNA clusters and families. An miRNA family may be located in one or more clusters, and a cluster may be involved in one or more families. Members of different families have been shown to be prone to appear in clusters, and vice versa. Reconstructed phylogenetic trees and networks may indicate potential evolutionary relationships, which also indicate duplication history in specific related gene clusters and families. Related miRNA families are always found to share common target mRNAs and biological pathways. Some clusters containing non-homologous miRNAs also tend to be clustered together as well as homologous miRNAs. In the present work, it is shown that homologous miRNAs are prone to appear in clusters based on functional and evolutionary pressures. The phenomenon of miRNA clusters containing homologous or genetic relationships is quite common. The integrative evolutionary analysis will provide more potential evolutionary and functional relationships between homologous and clustered miRNAs.
Display omitted
•62.22% of clusters have been shown to be involved in homologous miRNA genes.•Multicopy pre-miRNAs and sense/antisense homologous miRNAs are popular.•Homologous miRNAs are prone to appear in clusters, and vice versa.•Non-homologous clustered miRNAs tend to be clustered in phylogenetic tree.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This study sought to clarify the role of Runt-related transcription factor 1's (RUNX1's) regulation of downstream circular ribonucleic acid (circRNA) in the occurrence and development of papillary ...thyroid carcinoma (PTC) and to explore its mechanism of action.
The levels of RUNX1 were analyzed in PTC tumor tissues and adjacent non-tumor tissues in different types and at different stages via reverse-transcription quantitative polymerase chain reaction (RT-qPCR). The expression pattern and functional role of RUNX1 were analyzed in PTC cells via RT-qPCR, Western blotting, and Transwell assays. This study explored the differential expression of circRNA and microRNA (miRNA) in cells after knocking down RUNX1 through high-throughput sequencing and examined the changes in downstream signaling pathways through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses.
RUNX1 was upregulated in PTC tissues, and the expression levels of RUNX1 were related to PTC stage. The knockdown of RUNX1 inhibited the proliferation, migration, and invasion of cells. The high-throughput sequencing results showed that after RUNX1 knockdown, 29 circRNAs (11 upregulated and 18 downregulated) and 20 miRNAs (8 upregulated and 12 downregulated) had the most significant differential expression. The GO analysis of the differential circRNA downstream genes showed that the iron channel-related pathways, endosomal transport, learning, and memory pathways had the largest number of differential genes, and the most significant changes. The KEGG analysis showed that there were 2 pathways with P values <0.05; that is, the glycosaminoglycan synthesis and transcription dysregulation pathways. The GO analysis of the differential miRNA downstream genes showed that the protein binding and cytoplasmic pathways had the largest number of differential genes and the greatest level of difference. The KEGG analysis showed that the tumor-related pathways, phosphatidylinositol-3-kinase and protein kinase B, glycoprotein, cytoskeleton, Ras, and Rap1 pathways changed the most significantly.
RUNX1 is highly expressed in PTC. We conducted high-throughput sequencing to analyze the effect of knocking down RUNX1 on the levels of circRNA and miRNA in PTC. The GO and KEGG analyses revealed that the iron channel-related pathways, endosomal transport, learning and memory, glycosaminoglycan synthesis, and transcriptional disorder-related signaling pathways were enriched.
Of the approximately ~2.65 × 10³ mature microRNAs (miRNAs) so far identified in Homo sapiens, only a surprisingly small but select subset-about 35-40-are highly abundant in the human central nervous ...system (CNS). This fact alone underscores the extremely high selection pressure for the human CNS to utilize only specific ribonucleotide sequences contained within these single-stranded non-coding RNAs (ncRNAs) for productive miRNA-mRNA interactions and the down-regulation of gene expression. In this article we will: (i) consolidate some of our still evolving ideas concerning the role of miRNAs in the CNS in normal aging and in health, and in sporadic Alzheimer's disease (AD) and related forms of chronic neurodegeneration; and (ii) highlight certain aspects of the most current work in this research field, with particular emphasis on the findings from our lab of a small pathogenic family of six inducible, pro-inflammatory, NF-κB-regulated miRNAs including miRNA-7, miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155. This group of six CNS-abundant miRNAs significantly up-regulated in sporadic AD are emerging as what appear to be key mechanistic contributors to the sporadic AD process and can explain much of the neuropathology of this common, age-related inflammatory neurodegeneration of the human CNS.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The white-spot disease caused by marine ciliate Cryptocryon irritans hindered the sustainable development of large yellow croaker Larimichthys crocea industry. Better understandings about the ...parasite-host interactions in the molecular level will facilitate the prevention of mass mortality of the L. crocea caused by white-spot disease. MicroRNAs (miRNAs) are a class of small RNA molecules about 20–22 nucleotides which post-transcriptionally regulated many protein-coding genes and involved in many biological processes, especially in host-pathogen responses. In this study, we identified known and novel miRNAs in the gill and liver of L. crocea challenged by C. irritans by high throughput sequencing using Solexa technology. The data were further studied to screen differentially expressed miRNAs, and predict their target genes. The differential expression (p < 0.05) between libraries was observed in 103 miRNAs in liver tissue, among which 65 and 38 were conserved and novel miRNAs, 67 and 36 were up- and down-regulated miRNAs. While in gill tissue, 122 significant differentially expressed miRNAs were identified, among which 83 and 39 were conserved and novel miRNAs, 79 and 43 were up- and down-regulated miRNAs. In addition, these differentially expressed miRNAs target a series of genes which involved in many important biological processes including immune response. Here via deep sequencing, we for the first time characterize L. crocea miRNAs in response to C. irritans challenge, the results should help for better understandings about the immune response of the L. crocea under C. irritans challenge.
•We analyzed the liver and gill miRNAs of L. crocea under C. irritans challenge using miRNA-seq.•We predicted the immune-related signal pathway in liver and gill tissues of L. crocea under C. irritans challenge.•The results indicate two of different immune response models in the liver and gill tissues of L. crocea under C. irritans challenge.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
You have reached the maximum number of search results that are displayed.
For better performance, the search offers a maximum of 1,000 results per query (or 50 pages if the option 10/page is selected).
Consider using result filters or changing the sort order to explore your results further.
PDF
