FDPS-regulated transcriptome profile revealed its potential functions in osteoporosis as an RNA binding protein
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ABSTRACT:
PROVIDER: PRJNA636530 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11905572_1.fastq.gz | Fastqsanger.gz | |||
| SRR11905572_2.fastq.gz | Fastqsanger.gz | |||
| SRR11905573_1.fastq.gz | Fastqsanger.gz | |||
| SRR11905573_2.fastq.gz | Fastqsanger.gz | |||
| SRR11905574_1.fastq.gz | Fastqsanger.gz |
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Project description:Farnesyl diphosphate synthase (FDPS), an essencial enzyme involved in mevalonate pathway, is implicated in cancers and osteoporosis by catalyzing head to tail condensation of two molecules of isopentenyl pyrophosphate with dimethylallyl pyrophosphate to form farnesyl pyrophosphate. It has also been identified as an RNA-binding protein (RBP). However, it’s exactly RNA-binding function in diseases, up to now, remain unknown. In the present study, the function of FDPS in HeLa cells was investigated with FDPS overexpression. The results showed that FDPS overexpression promoted proliferation in HeLa cells. FDPS overexpression extensively regulated the expression of genes in cell proliferation, cytokine-mediated signaling pathway, and extracellular matrix organization. In addition, FDPS extensively regulated the alternative splicing of numbers of genes related with osteoporosis, including NAB1, FGFR3, and ALPL, and FDPS-regulated DEGs and ASEs were highly validated by RT-qPCR. This is the first study to investigate the properties of FDPS as an RBP from a genome-wide perspective, our results suggested that FDPS acts as an RBP playing an important role in cancer progression and osteoporosis by altering gene expression and regulating alternative splicing, which contributes to a precise understanding of potentially FDPS-targeted therapies.
2023-02-06 | GSE151605 | GEO
Project description:Recent studies have shown that microRNAs (miRNAs) are implicated in the development of postmenopausal osteoporosis, implying potential biomarkers. We performed a microarray-based expression scanning to search for potential circulating miRNA biomarkers for postmenopausal osteoporosis as whole blood obtianed from patients was used. MiRNA expression in the whole blood of 23 Chinese postmenopausal women with osteopenia and that of 25 Chinese postmenopausal women with osteoporosis. After total RNA was extracted, all of the RNA extraction samples were seperately pooled into six subgroups according to the T-score measurement.
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Project description:Recent studies have shown that microRNAs (miRNAs) are implicated in the development of postmenopausal osteoporosis, implying potential biomarkers. We performed a microarray-based expression scanning to search for potential circulating miRNA biomarkers for postmenopausal osteoporosis as whole blood obtianed from patients was used.
2014-12-23 | GSE64433 | GEO
Project description:Background: Osteoporosis is one of the most common chronic diseases around the world, especially in postmenopausal women. Circular RNAs (circRNAs) are emerging as important regulators in human disease. The aim of the present study was to analyze circRNA expression profiles in osteoporosis and to explore the clinical significance. Methods: The serum samples were collected from osteoporosis patients and healthy people. The circRNA array was performed to screen for differentially expressed circRNAs. The mRNA expression levels of target genes were analyzed by quantitative real-time PCR (qRT-PCR). Results: Hsa_circ_0006859 was identified as one of the most upregulated circRNAs in the microarray analysis. Hsa_circ_0006859 in exosome was upregulated in osteoporosis patients compared with healthy controls. Hsa_circ_0006859 could differentiate osteopenia or osteoporosis patients from healthy controls with high sensitivity and specificity. Conclusion: Exosomal hsa_circ_0006859 is a potential biomarker for postmenopausal osteoporosis.
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Project description:Identification of exosomal circRNAs as potential biomarkers for postmenopausal osteoporosis
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Project description:Osteoporosis is a metabolic bone disease characterized by a decrease in bone mass and degradation of the bone microstructure, which increases bone fragility and risk of fracture. However, the molecular mechanisms of osteoporosis remain unclear. The current study attempts to elucidate the role of exosomal long noncoding RNA in the pathology of osteoporosis. Peripheral blood was collected from persons with (OP) or without (NC) osteoporosis, and the serum exosomes were extracted using ultra centrifugation process. Total RNA of exosomes was isolated, and the lncRNAs profiling was done using RNA-Seq experiments. In silico analysis resulted in identification of 393 differentially expressed (DE) lncRNAs in OP vs NC, with 296 that were up-regulated and 97 were down-regulated. Bioinformatics analysis of potential target mRNAs of lncRNAs with cis-acting mechanism showed that mRNAs co-located with DE lncRNAs were highly enriched in osteoporosis-related pathways, including regulation of insulin secretion, activation of MAPK activity, cellular response to metal ions, fucosylation and proteolysis. Together these results suggest that lncRNAs of serum exosomes could play a significant role in development of osteoporosis and such information may be helpful in developing diagnostic markers and therapeutic modules for osteoporosis.
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Project description:Osteoporosis is a significant health concern, and the role of microRNAs (miRNAs) in cell growth and development regulation is well recognized. High-throughput sequencing technology is widely employed in current research. This study aimed to identify and validate miRNAs associated with osteoporosis. Bone specimens were collected from patients with osteoporosis (n=3) and without osteoporosis (n=3). High-throughput sequencing was utilized to screen for miRNAs, followed by analysis using volcano maps, Wayne maps, gene ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The identified miRNAs were further confirmed using qRT-PCR. Sequencing analysis revealed 12 down-regulated and five upregulated miRNAs in osteoporosis. GO and KEGG analysis indicated the association of these miRNAs with bone metabolism. qRT-PCR results demonstrated a significant decrease in miR-140-5p, miR-127-3p, miR-199b-5p, miR-181a-5p, miR-181d-5p, and miR-542-3p (all P<0.05) in osteoporosis compared to controls, while miR-486-3p and miR-486-5p exhibited a significant increase (P<0.05). This study utilized high-throughput sequencing to identify differential miRNA expression in individuals with osteoporosis. Specifically, six miRNAs (miR-140-5p, miR-127-3p, miR-199b-5p, miR-181a-5p, miR-181d-5p, and miR-542) showed decreased expression, whereas two miRNAs (miR-486-3p and miR-486-5p) exhibited increased expression. The differential expression of these miRNAs may serve as predictive indicators, potentially aiding in the prognosis and management of osteoporosis.
2024-08-28 | GSE273345 | GEO
Project description:Osteoporosis is caused by imbalanced bone remodelling homeostasis and is highly prevalent in post-menopausal women. The impact of osteoporosis on mesenchymal stromal cells (MSCs) is a key area of research as they are the progenitors of osteoblasts and are therefore critical to bone homeostasis. TBioinformatic analysis of transcriptional profiling data revealed specific misregulation of genes involved in the processing and trafficking of cellular components, as well as downregulation of Neo1 which has an important role in controlling cell fate choice. These data indicate that the therapeutic targeting of bone marrow MSCs to increase their numbers, to support the appropriate processing of cellular contents, or to redirect cell fate choice may provide new methods for the treatment of osteoporosis, thereby reducing fracture-associated morbidity and improving quality of life for the 200 million people living with osteoporosis globally.
2024-04-09 | GSE189524 | GEO
Project description:To explore the variation of serum microRNA expression during osteoporosis, we have employed microRNA microarray expression profiling as a discovery platform to identify microRNAs with the potential to diagnose osteoporosis from healthy and osteopenia individuals for clinical use. Whole blood from healthy, osteopenic and osteoporotic donors was collected, and the sera were separated. Twenty two microRNAs (miR-15a-5p, miR-29b-5p, miR-30c-2-3p, miR-145-5p, miR-199a-5p, miR-301a-3p, miR-424-5p, miR-497-5p, miR-526b-5p, miR-550a-5p, miR-575, miR-654-5p, miR-663a, miR-708-5p, miR-877-3p, miR-1246, miR-1260b, miR-1299, miR-1323, miR-4447, miR-4769-3p and miR-5685) were finally used for further detection of osteoporosis diagnosis.
2019-12-08 | GSE91033 | GEO
Project description:The development of predictive markers to determine the tipping point prior to the onset of osteoporosis is essential to mitigate further irrevocable deterioration. In order to determine the early warning signs before osteoporosis, we used the dynamic network biomarker (DNB) approach to analyze the time series gene expression data in the zebrafish osteoporosis model and revealed that cyclin-dependent kinase inhibitor 1A (cdkn1a) is one core member of DNB. We demonstrated that cdkn1a negatively regulates osteogenesis, evidenced by the loss-of-function and gain-of-function studies. On one hand, CRISPR/Cas9-mediated cdkn1a knockout in the zebrafish significantly altered skeletal development and increased bone mineralization. On the other hand, inducible cdkn1a expression significantly contributed to the osteoclast differentiation. We also provide mechanistic clues that cdkn1a participates in osteoclast differentiation by regulating its upstream signaling cascades. Our data provided new insights into the dynamic nature of osteoporosis, and identified cdkn1a as the early-warning signals of osteoporosis onset.
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