Transcriptomic Data Identified Key Transcription Factors for Osteoporosis in Caucasian Women.
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ABSTRACT:
SUBMITTER: Zhou Y
PROVIDER: S-EPMC6343666 | biostudies-literature | 2018 Dec
REPOSITORIES: biostudies-literature
Publications
Transcriptomic Data Identified Key Transcription Factors for Osteoporosis in Caucasian Women.
Zhou Yu Y Zhu Wei W Zhang Lan L Zeng Yong Y Xu Chao C Tian Qing Q Deng Hong-Wen HW
Calcified tissue international 20180728 6
Osteoporosis is a prevalent bone metabolic disease, mainly caused by excessive bone resorption (by osteoclasts) over bone formation (by osteoblasts). Identifying the key transcription factors and understanding the regulatory network influencing osteoclastogenesis will be helpful to explore the potential biological mechanism for osteoporosis. In our study, peripheral blood monocyte (PBM) was used as a cell model for bone mineral density (BMD) research. PBMs serve as progenitors of osteoclasts and ...[more]
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Project description:INTRODUCTION:Osteoporosis is a prevalent bone metabolic disease characterized by bone fragility. As a key pathophysiological mechanism, the disease is caused by excessive bone resorption (by osteoclasts) over bone formation (by osteoblasts). Peripheral blood monocytes (PBMs) is a major systemic cell model for bone metabolism by serving as progenitors of osteoclasts and producing cytokines important for osteoclastogenesis. Protein-coding genes for osteoporosis have been widely studied by mRNA analyses of PBMs in high versus low hip bone mineral density (BMD) subjects. However, long noncoding RNAs (lncRNAs), which account for a large proportion of human transcriptome, have seldom been studied. METHODS:In this study, microarray analyses of monocytes were performed using Affymetrix exon 1.0 ST arrays in 73 Caucasian females (age: 47-56). LncRNA profile was generated by re-annotating exon array for lncRNAs detection, which yielded 12,007 lncRNAs mapped to the human genome. RESULTS:575 lncRNAs were differentially expressed between the two groups. In the high BMD subjects, 309 lncRNAs were upregulated and 266 lncRNAs were downregulated (nominally significant, raw p-value?<?0.05). To investigate the relationship between mRNAs and lncRNAs, we used two approaches to predict the target genes of lncRNAs and found that 26 candidate lncRNAs might regulate mRNA expression. The majority of these lncRNAs were further validated to be potentially correlated with BMD by GWAS analysis. CONCLUSION:Overall, our findings for the first time reported the lncRNAs profiles for osteoporosis and suggested the potential regulatory mechanism of lncRNAs on protein-coding genes in bone metabolism.
| S-EPMC6712977 | biostudies-literature
Project description:ObjectiveTo bridge the efficacy and compare the safety of the 24-week teriparatide treatment in a Chinese osteoporosis study (NCT00414973) to a large international trial (FPT, NCT00670501) to determine whether long-term results from the international study were applicable to Chinese patients.MethodsIn this post-hoc analysis, a propensity score matching method was used to select patients with similar baseline characteristics. Patients were female with osteoporosis at high risk of fracture, aged ≥55 years, and had no history of rheumatoid arthritis or corticosteroid use. Outcomes included percentage changes in lumbar-spine bone mineral density (LS-BMD) from baseline to 24 weeks, safety in matched-pair patients, and long-term percentage changes in LS-BMD and fragility fracture incidence in the matched fracture prevention trial (FPT) population. The determination of the acceptability of bridging results was based on the International Conference on Harmonization E5 guidelines.ResultsA total number of 228 patients from each study were matched and paired. Patients were similar at baseline (P-values >0.33) except for ethnicity (98% Caucasian for FPT). For changes in LS-BMD from baseline to week 24, treatment with teriparatide showed significantly greater increases (P-values <0.001; least-squares mean difference: 5.0% in the Chinese study and 5.4% in FPT) than comparator (calcitonin/placebo). The safety profiles over 24 weeks were similar between two studies. For matched-pair FPT patients, long-term changes in LS-BMD were significantly greater (least-squares mean difference: 11.5%, P<0.001) and the fragility fracture rate was marginally lower in the teriparatide group compared with the placebo group (13.1% vs 22.3%, P=0.070).ConclusionAssuming similar pharmacokinetic profiles for teriparatide between populations, comparable increases in LS-BMD and consistent safety profiles within 24 weeks of the treatment suggest long-term LS-BMD results from the FPT may be applicable to Chinese population.
| S-EPMC6542327 | biostudies-literature
Project description:BACKGROUND: Transcription factors (TFs) contain DNA-binding domains (DBDs) and regulate gene expression by binding to specific DNA sequences. In addition, there are proteins, called transcription coregulators (TCs), which lack DBDs but can alter gene expression through interaction with TFs or RNA Polymerase II. Therefore, it is interesting to identify and classify the TFs and TCs in a genome. In this study, maize (Zea mays) and foxtail millet (Setaria italica), two important species for the study of C4 photosynthesis and kranz anatomy, were selected. RESULT: We conducted a comprehensive genome-wide annotation of TFs and TCs in maize B73 and in two strains of foxtail millet, Zhang gu and Yugu1, and classified them into families. To gain additional support for our predictions, we searched for their homologous genes in Arabidopsis or rice and studied their gene expression level using RNA-seq and microarray data. We identified many new TF and TC families in these two species, and described some evolutionary and functional aspects of the 9 new maize TF families. Moreover, we detected many pseudogenes and transposable elements in current databases. In addition, we examined tissue expression preferences of TF and TC families and identified tissue/condition-specific TFs and TCs in maize and millet. Finally, we identified potential C4-related TF and TC genes in maize and millet. CONCLUSIONS: Our results significantly expand current TF and TC annotations in maize and millet. We provided supporting evidence for our annotation from genomic and gene expression data and identified TF and TC genes with tissue preference in expression. Our study may facilitate the study of regulation of gene expression, tissue morphogenesis, and C4 photosynthesis in maize and millet. The data we generated in this study are available at http://sites.google.com/site/jjlmmtf.
| S-EPMC4189582 | biostudies-literature
Project description:BackgroundOsteoporosis (OP) is a systemic disease with bone loss and microstructural deterioration. Numerous noncoding RNAs (ncRNAs) have been proved to participate in various diseases, especially circular RNAs (circRNAs). However, the expression profile and mechanisms underlying circRNAs in male osteoporosis have not yet been explored.MethodsThe whole transcriptome expression profile and differences in mRNAs, circRNAs, and microRNAs (miRNAs) were investigated in peripheral blood samples of patients with osteoporosis and healthy controls consisting of males ≥ 60-years-old.ResultsA total of 398 circRNAs, 51 miRNAs, and 642 mRNAs were significantly and differentially expressed in osteoporosis compared to healthy controls. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the host genes of significantly differentially expressed circRNAs were mainly enriched in the regulation of cell cycle process: biological process (BP), organelle part cellular components (CC), protein binding molecular function (MF), Toll-like receptor signaling pathway, tumor necrosis factor (TNF) signaling pathway, and thyroid hormone signaling pathway. circRNA-miRNA-mRNA regulatory network was constructed using the differentially expressed RNAs. Moreover, key circRNAs (hsa_circ_0042409) in osteoporosis were discovered and validated by qPCR.ConclusionsThe key cicrRNAs plays a major role in the pathogenesis of osteoporosis and could be used as potential biomarkers or targets in the diagnosis and treatment of osteoporosis.
| S-EPMC8164409 | biostudies-literature
Project description:Background: Osteoporosis (OP) is a systemic disease with bone loss and microstructural deterioration. Numerous noncoding RNAs have been proved to participate in various diseases, especially for circular RNAs (circRNAs). However, the expression profile and hidden mechanisms of circRNAs in male osteoporosis have not been explored yet. Methods: Here we investigated the whole transcriptome expression profile and differences of mRNAs, circRNAs and miRNAs in peripheral blood samples of patients with osteoporosis and healthy controls of male with age larger than 60 years old. Results: A total of 398 circRNAs, 51 miRNAs and 642 mRNAs were identified that were significant differentially expressed in osteoporosis compared with healthy controls. GO and KEGG enrichment analysis showed the host genes of significantly differentially expressed circRNAs were mainly enriched in regulation of cell cycle process BP, organelle part CC, protein binding MF and Toll-like receptor signaling pathway, TNF signaling pathway and Thyroid hormone signaling pathway. circRNA-miRNA-mRNA regulatory network was constructed using the differentialy expressed RNAs. Moreover, key circRNAs in osteoporosis were discovered further and validated by qPCR, such as hsa_circ_0042409. Those key cicrRNAs may play an important role in the pathogenesis of osteoporosis and could be used as potential biomarkers or targets in the diagnosis and treatment of osteoporosis.
2020-10-07 | GSE159121 | GEO
Project description:The current study aimed to isolate key transcription factors (TFs) in caerulein-induced pancreatitis, and to identify the difference between wild type and Mist1 knockout (KO) mice, in order to elucidate the contribution of Mist1 to pancreatitis. The gene profile of GSE3644 was downloaded from the Gene Expression Omnibus database then analyzed using the t-test. The isolated differentially expressed genes (DEGs) were mapped into a transcriptional regulatory network derived from the Integrated Transcription Factor Platform database and in the network, the interaction pairs involving at least one DEG were screened. Fisher's exact test was used to analyze the functional enrichment of the target genes. A total of 1,555 and 3,057 DEGs were identified in the wild type and Mist1KO mice treated with caerulein, respectively. DEGs screened in Mist1KO mice were predominantly enriched in apoptosis, mitogen-activated protein kinase signaling and other cancer-associated pathways. A total of 188 and 51 TFs associated with pathopoiesis were isolated in Mist1KO and wild type mice, respectively. Out of the top 10 TFs (ranked by P-value), 7 TFs, including S-phase kinase-associated protein 2 (Skp2); minichromosome maintenance complex component 3 (Mcm3); cell division cycle 6 (Cdc6); cyclin B1 (Ccnb1); mutS homolog 6 (Msh6); cyclin A2 (Ccna2); and cyclin B2 (Ccnb2), were expressed in the two types of mouse. These TFs were predominantly involved in phosphorylation, DNA replication, cell division and DNA mismatch repair. In addition, specific TFs, including minichromosome maintenance complex component 7 (Mcm7); lymphoid-specific helicase (Hells); and minichromosome maintenance complex component 6 (Mcm6), that function in the unwinding of DNA were identified to participate in Mist1KO pancreatitis. The DEGs, including Cdc6, Mcm6, Msh6 and Wdr1 are closely associated with the regulation of caerulein-induced pancreatitis. Furthermore, other identified TFs were also involved in this type of regulation.
| S-EPMC4464163 | biostudies-literature
Project description:BACKGROUND: Osteoporosis is an important public health problem in older adults. It is more common in postmenopausal women and not only gives rise to morbidity but also markedly diminishes the quality of life in this population. There is lack of information about the risk factor of osteoporosis in developing countries. In this study we aimed to assess the risk factors for osteoporosis in postmenopausal women from selected BMD centers of two developing Asian countries (Iran and India). METHODS: This study is a multicenter interview-based study conducted in selected hospitals and health centers from urban areas in Iran and India. The case group included postmenopausal osteoporotic women who were identified as patients with bone density higher than 2.5 SD below average of young normal bone density (in L1-L4) spine region interest and/or total femoral region) by using DEXA method. The controls were chosen from postmenopausal women with normal bone density (in L1-L4 spine and total femoral regions using DEXA method) matching in age groups was strategy of choice.The sample sizes included from Iran a total of 363 subjects (178 osteoporotic and 185 normal) and from India a total of 354 subjects (203 osteoporotic and 151 normal). RESULTS: The significant (p < 0.05) risk factors in present study population with their Odds Ratios (in parenthesis, respectively in Iran and India) were as follow:Lower education defined as less than class 12 or nil college (2.1) (2.7), duration of menopause greater than 5 years: (2.2) (1.4), Menarche age (after 14 years): (1.9) (1.6), Menopause age (before 45 years): (1.1) (2), Parity more than 3: (1.1) (1), Bone and joint problem (2.3) (2.2). Calcium supplementation (0.6) and HRT (0.4) were shown as protective factors and steroid therapy (3.3) was found as a risk factor in Iran. Calcium supplementation more than 1 year (0.3) was shown as a protective factor in India.Pure vegetarianism: (2.2) and Red meat consumption more than 4 times per week (1.4) was shown as a risk factor in Indian and Iranian subjects respectively. Regular consumption of Soya (0.3), almond (0.5), fish (0.5), fruits (0.4) and milk tea 4 cups per day and more (0.4) appeared to be significant protective factors in India. Regular consumption of cheese (0.5), milk (0.5), chicken (0.4), egg (0.6), fruit (0.4), tea 7 cups per day and more (0.3) were found to be significant protective factors in Iran. Exercises were shown as protective factor in Iran (0.4) and India (0.4). There were no significant differences in association of risk factors and osteoporosis between Iranian and Indian subjects. CONCLUSION: Osteoporosis in Iranian and Indian subjects also appears to be associated with several known risk factors that well described in the literature. There were no significant differences in association of risk factors and osteoporosis between Iranian and Indian subjects. It was shown a protective role of certain nutritional dietary components and also exercises in both populations and can be exploited in preventive educational strategies on osteoporosis in these populations.
| S-EPMC2289820 | biostudies-other
Project description:Thyroid nodules are present in upto 50% of the population worldwide, and thyroid malignancy occurs in only 5-15% of nodules. Until now, fine-needle biopsy with cytologic evaluation remains the diagnostic choice to determine the risk of malignancy, yet it fails to discriminate as benign or malignant in one-third of cases. In order to improve the diagnostic accuracy and reliability, molecular testing based on transcriptomic data has developed rapidly. However, gene signatures of thyroid nodules identified in a plenty of transcriptomic studies are highly inconsistent and extremely difficult to be applied in clinical application. Therefore, it is highly necessary to identify consistent signatures to discriminate benign or malignant thyroid nodules. In this study, five independent transcriptomic studies were combined to discover the gene signature between benign and malignant thyroid nodules. This combined dataset comprises 150 malignant and 93 benign thyroid samples. Then, there were 279 differentially expressed genes (DEGs) discovered by the feature selection method (Student's t test and fold change). And the weighted gene co-expression network analysis (WGCNA) was performed to identify the modules of highly co-expressed genes, and 454 genes in the gray module were discovered as the hub genes. The intersection between DEGs by the feature selection method and hub genes in the WGCNA model was identified as the key genes for thyroid nodules. Finally, four key genes (ST3GAL5, NRCAM, MT1F, and PROS1) participated in the pathogenesis of malignant thyroid nodules were validated using an independent dataset. Moreover, a high-performance classification model for discriminating thyroid nodules was constructed using these key genes. All in all, this study might provide a new insight into the key differentiation of benign and malignant thyroid nodules.
| S-EPMC8795894 | biostudies-literature
Project description:Accurate prediction of gene regulatory rules is important towards understanding of cellular processes. Existing computational algorithms devised for bulk transcriptomics typically require a large number of time points to infer gene regulatory networks (GRNs), are applicable for a small number of genes and fail to detect potential causal relationships effectively. Here, we propose a novel approach 'TENET' to reconstruct GRNs from single cell RNA sequencing (scRNAseq) datasets. Employing transfer entropy (TE) to measure the amount of causal relationships between genes, TENET predicts large-scale gene regulatory cascades/relationships from scRNAseq data. TENET showed better performance than other GRN reconstructors, in identifying key regulators from public datasets. Specifically from scRNAseq, TENET identified key transcriptional factors in embryonic stem cells (ESCs) and during direct cardiomyocytes reprogramming, where other predictors failed. We further demonstrate that known target genes have significantly higher TE values, and TENET predicted higher TE genes were more influenced by the perturbation of their regulator. Using TENET, we identified and validated that Nme2 is a culture condition specific stem cell factor. These results indicate that TENET is uniquely capable of identifying key regulators from scRNAseq data.
| S-EPMC7797076 | biostudies-literature
Project description:BackgroundLung adenocarcinoma (LUAD) is one of the most common cancers worldwide. The etiology and pathophysiology of LUAD remain unclear. The aim of the present study was to identify the key genes, miRNAs and transcription factors (TFs) associated with the pathogenesis and prognosis of LUAD.MethodsThree gene expression profiles (GSE43458, GSE32863, GSE74706) of LUAD were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by GEO2R.The Gene Ontology (GO) terms, pathways, and protein-protein interactions (PPIs) of these DEGs were analyzed. Bases on DEGs, the miRNAs and TFs were predicted. Furthermore, TF-gene-miRNA co-expression network was constructed to identify key genes, miRNAs and TFs by bioinformatic methods. The expressions and prognostic values of key genes, miRNAs and TFs were carried out through The Cancer Genome Atlas (TCGA) database and Kaplan Meier-plotter (KM) online dataset.ResultsA total of 337 overlapped DEGs (75 upregulated and 262 downregulated) of LUAD were identified from the three GSE datasets. Moreover, 851 miRNAs and 29 TFs were identified to be associated with these DEGs. In total, 10 hub genes, 10 key miRNAs and 10 key TFs were located in the central hub of the TF-gene-miRNA co-expression network, and validated using The Cancer Genome Atlas (TCGA) database. Specifically, seven genes (PHACTR2, MSRB3, GHR, PLSCR4, EPB41L2, NPNT, FBXO32), two miRNAs (hsa-let-7e-5p, hsa-miR-17-5p) and four TFs (STAT6, E2F1, ETS1, JUN) were identified to be associated with prognosis of LUAD, which have significantly different expressions between LUAD and normal lung tissue. Additionally, the miRNA/gene co-expression analysis also revealed that hsa-miR-17-5p and PLSCR4 have a significant negative co-expression relationship (r=?0.33, P=1.67e-14) in LUAD.ConclusionsOur study constructed a regulatory network of TF-gene-miRNA in LUAD, which may provide new insights about the interaction between genes, miRNAs and TFs in the pathogenesis of LUAD, and identify potential biomarkers or therapeutic targets for LUAD.
| S-EPMC7330310 | biostudies-literature