scholarly journals Integrated Genome-Wide Methylation and Expression Analyses Reveal Key Regulators in Osteosarcoma

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Fei Wang ◽  
Guoqing Qin ◽  
Junzhi Liu ◽  
Xiunan Wang ◽  
Baoguo Ye

Osteosarcoma (OS) is one of the most common types of primary bone tumors in early adolescence with unsatisfied prognosis. Aberrant DNA methylation had been demonstrated to be related to tumorigenesis and progression of multiple cancers and could serve as the potential biomarkers for the prognosis of human cancers. In conclusion, this study identified 18 downregulated hypomethylation genes and 52 upregulated hypomethylation genes in OS by integrating the analysis the GSE97529 and GSE42572 datasets. Bioinformatics analysis revealed that OS-specific methylated genes were involved in regulating multiple biological processes, including chemical synaptic transmission, transcription, response to drug, and regulating immune response. KEGG pathway analysis showed that OS-specific methylated genes were associated with the regulation of Hippo, cAMP calcium, MAPK, and Wnt signaling pathways. By analyzing R2 datasets, this study showed that the dysregulation of these OS-specific methylated genes was associated with the metastasis-free survival time in patients with OS, including CBLN4, ANKMY1, BZW1, KRTCAP3, GZMB, KRTDAP, LY9, PFKFB2, PTPN22, and CLDN7. This study provided a better understanding of the molecular mechanisms underlying the progression and OS and novel biomarkers for the prognosis of OS.

2021 ◽  
Author(s):  
Letian Zhang ◽  
Tingjun Liu ◽  
Chengzhang Hu ◽  
Xuan Zhang ◽  
Qin Zhang ◽  
...  

Abstract Background Fatty liver disease prevalently occurs in commercial postpartum dairies, resulting in a worldwide high culling rate because of their subsequent limitations of production and reproduction performance. Results Fatty liver-specific proteome and acetylome analysis revealed that energy metabolism suppression closely associated with mitochondrial dysfunction and inflammation activation are shown to be remarkable biological processes underlying the development of fatty liver disease, thereby acetylation modification of proteins modulating these processes. Twenty pivotal genetic factors/genes that differentially expressing and being acetylation modified in liver were identified and proposed to regulate the pathogenesis of fatty liver dairies. These proteins were confirmed to be differentially expressing in individual liver tissues, eight of which being validated through immunohistochemistry assay. Conclusion This study provided a comprehensive proteome and acetylome profile of fatty liver of dairy cows, and revealed potential important biological processes and essential regulators in the pathogenesis of fatty liver disease. Expectantly, understanding the molecular mechanisms of the pathogenesis of fatty liver disease in dairies, as an animal model of non-alcoholic fatty liver disease (NAFLD) in human beings, which is a clinico-pathologically defined process associated with metabolic syndrome, could inspire and facilitate the development of efficacious therapeutic drugs on NAFLD.


2019 ◽  
Vol 14 ◽  
Author(s):  
Lishui Shen ◽  
Guilin Shen ◽  
Xiaoli Lu ◽  
Guomin Ding ◽  
Xiaofeng Hu

Atrial fibrillation (AF) is one of the most common heart arrhythmic disorders all over the world. However, it is worth noting that the mechanism underlying AF is still dimness. In this study, we implemented a series of bioinformatics methods to explore the mechanisms of lncRNAs underlying AF pathogenesis. The present study analyzed the public datasets (GSE2240 and GSE115574) to identify differentially expressed long non-coding RNAs (lncRNAs) and mRNAs in the progression of AF. Totally, 71 differentially expressed lncRNAs and 390 DEGs were identified in AF.Next, we performed bioinformatics analyses to explore the functions of lncRNAs in AF. Gene Ontology (GO) analysis indicated that differentially expressed lncRNAs were involved in regulating multiple key biological processes, such as cell cycle and signal transduction. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated these lncRNAs were associated with the regulation of MAPK and Wnt signaling pathways. Eight lncRNAs (RP5-1154L15.2, RP11-339B21.15, RP11-448A19.1, RP11-676J12.4, LOC101930415, MALAT1, NEAT1, and PWAR6) were identified to be key lncRNAs and widely co-expressed with a series of differentially expressed genes (DEGs). Although further validation was still needed, our study may be helpful to elucidate the mechanisms of lncRNAs underlying AF pathogenesis and providing further insight into identifying novel biomarkers for AF.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Xiangxiang Zhou ◽  
Linquan Zhan ◽  
Kai Huang ◽  
Xin Wang

Abstract With covalently closed circular structures, circular RNAs (circRNAs) were once misinterpreted as by-products of mRNA splicing. Being abundant, stable, highly conserved, and tissue-specific, circRNAs are recently identified as a type of regulatory RNAs. CircRNAs bind to certain miRNAs or proteins to participate in gene transcription and translation. Emerging evidence has indicated that the dysregulation of circRNAs is closely linked to the tumorigenesis and treatment response of hematological malignancies. CircRNAs play critical roles in various biological processes, including tumorigenesis, drug resistance, tumor metabolism, autophagy, pyroptosis, and ferroptosis. The N6-methyladenosine modification of circRNAs and discovery of fusion-circRNAs provide novel insights into the functions of circRNAs. Targeting circRNAs in hematological malignancies will be an attractive treatment strategy. In this review, we systematically summarize recent advances toward the novel functions and molecular mechanisms of circRNAs in hematological malignancies, and highlight the potential clinical applications of circRNAs as novel biomarkers and therapeutic targets for future exploration.


2015 ◽  
Vol 112 (34) ◽  
pp. E4802-E4810 ◽  
Author(s):  
Dawn H. Nagel ◽  
Colleen J. Doherty ◽  
Jose L. Pruneda-Paz ◽  
Robert J. Schmitz ◽  
Joseph R. Ecker ◽  
...  

The circadian clock in Arabidopsis exerts a critical role in timing multiple biological processes and stress responses through the regulation of up to 80% of the transcriptome. As a key component of the clock, the Myb-like transcription factor CIRCADIAN CLOCK ASSOCIATED1 (CCA1) is able to initiate and set the phase of clock-controlled rhythms and has been shown to regulate gene expression by binding directly to the evening element (EE) motif found in target gene promoters. However, the precise molecular mechanisms underlying clock regulation of the rhythmic transcriptome, specifically how clock components connect to clock output pathways, is poorly understood. In this study, using ChIP followed by deep sequencing of CCA1 in constant light (LL) and diel (LD) conditions, more than 1,000 genomic regions occupied by CCA1 were identified. CCA1 targets are enriched for a myriad of biological processes and stress responses, providing direct links to clock-controlled pathways and suggesting that CCA1 plays an important role in regulating a large subset of the rhythmic transcriptome. Although many of these target genes are evening expressed and contain the EE motif, a significant subset is morning phased and enriched for previously unrecognized motifs associated with CCA1 function. Furthermore, this work revealed several CCA1 targets that do not cycle in either LL or LD conditions. Together, our results emphasize an expanded role for the clock in regulating a diverse category of genes and key pathways in Arabidopsis and provide a comprehensive resource for future functional studies.


Sarcoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Eisuke Kobayashi ◽  
Francis J. Hornicek ◽  
Zhenfeng Duan

Osteosarcoma (OS) is the most common primary malignant bone tumor, usually arising in the long bones of adolescents and young adults. While our knowledge of the molecular pathogenesis of OS has increased in recent years, we are still far from a comprehensive understanding of the molecular mechanisms of the disease, such as its tumorigenesis, specific mediators of disease progression, occurrence of chemoresistance, and development of metastasis. After the recent discovery of microRNAs (miRNAs), their critical roles in molecular biological processes have been of great interest in the cancer research field, including research on sarcomas. MiRNAs are highly conserved noncoding RNAs which play important roles as oncogenic or suppressive genes to simultaneously regulate multiple targets. Recent genome-wide screening using miRNA expression profiles has identified specific miRNA expression patterns that are associated with the biological and clinical properties of cancers. Additionally, miRNAs and their target genes or proteins can be potential novel biomarkers or therapeutic targets for cancer. However, there are several challenges that must be addressed in order to translate miRNA-based therapeutics to the clinical setting. In this review, we summarize the current understanding of the roles that miRNAs play in OS, and highlight their potential as biomarkers or therapeutic targets.


1982 ◽  
Vol 21 (04) ◽  
pp. 136-139 ◽  
Author(s):  
C.-J. Edeling

Whole-body scintigraphy with both 99mTc-phosphonate and 67Ga was performed on 92 patients suspected of primary bone tumors. In 46 patients with primary malignant bone tumors, scintigraphy with 99mTc-phosphonate disclosed the primary tumor in 44 cases and skeletal metastases in 11, and 67Ga scintigraphy detected the primary tumor in 43 cases, skeletal metastases in 6 cases and soft-tissue metastases in 8 cases. In 25 patients with secondary malignant bone tumors, bone scintigraphy visualized a single lesion in 10 cases and several lesions in 15 cases, and 67Ga scintigraphy detected the primary tumor in 17 cases, skeletal metastases in 17 cases and soft-tissue metastases in 9 cases. In 21 patients with benign bone disease positive uptake of 99mTc-phosphonate was recognized in 19 cases and uptake of 67Ga in 17 cases. It is concluded that bone scintigraphy should be used in patients suspected of primary bone tumors. If malignancy is suspected, 67Ga scintigraphy should be performed in addition.


2019 ◽  
Vol 65 (2) ◽  
pp. 165-171
Author(s):  
Aleksey Belyaev ◽  
Georgiy Prokhorov ◽  
Anna Arkhitskaya

A review of the literature shows that surgical procedures will remain the standard treatment for primary bone tumors. Analysis of studies on the assessment of long-term results shows that additional double cryogenic treatment of the curettage cavity can improve the treatment outcomes of patients with giant cell tumors, dysplastic diseases and some forms of malignant lesions. The traditional execution of the procedure is associated with the open installation of liquid nitrogen in the bone cavity, which requires special skills in handling aggressive refrigerant from the staff and does not exclude complications. In case of multiple metastatic bone lesions, surgical treatment is not indicated. The recent emergence in clinical practice of new equipment with a closed liquid nitrogen circulation circuit inside cryoprobes resumes interest in cryoabla-tion of bone tumor lesions using modern minimally invasive puncture cryotechnology and expanding indications for its use in patients with severe comorbidities.


2020 ◽  
Vol 27 ◽  
Author(s):  
Giulia De Riso ◽  
Sergio Cocozza

: Epigenetics is a field of biological sciences focused on the study of reversible, heritable changes in gene function not due to modifications of the genomic sequence. These changes are the result of a complex cross-talk between several molecular mechanisms, that is in turn orchestrated by genetic and environmental factors. The epigenetic profile captures the unique regulatory landscape and the exposure to environmental stimuli of an individual. It thus constitutes a valuable reservoir of information for personalized medicine, which is aimed at customizing health-care interventions based on the unique characteristics of each individual. Nowadays, the complex milieu of epigenomic marks can be studied at the genome-wide level thanks to massive, highthroughput technologies. This new experimental approach is opening up new and interesting knowledge perspectives. However, the analysis of these complex omic data requires to face important analytic issues. Artificial Intelligence, and in particular Machine Learning, are emerging as powerful resources to decipher epigenomic data. In this review, we will first describe the most used ML approaches in epigenomics. We then will recapitulate some of the recent applications of ML to epigenomic analysis. Finally, we will provide some examples of how the ML approach to epigenetic data can be useful for personalized medicine.


2019 ◽  
Vol 132 (23) ◽  
Author(s):  
Wenhui Zhou ◽  
Kayla M. Gross ◽  
Charlotte Kuperwasser

ABSTRACT The transcription factor Snai2, encoded by the SNAI2 gene, is an evolutionarily conserved C2H2 zinc finger protein that orchestrates biological processes critical to tissue development and tumorigenesis. Initially characterized as a prototypical epithelial-to-mesenchymal transition (EMT) transcription factor, Snai2 has been shown more recently to participate in a wider variety of biological processes, including tumor metastasis, stem and/or progenitor cell biology, cellular differentiation, vascular remodeling and DNA damage repair. The main role of Snai2 in controlling such processes involves facilitating the epigenetic regulation of transcriptional programs, and, as such, its dysregulation manifests in developmental defects, disruption of tissue homeostasis, and other disease conditions. Here, we discuss our current understanding of the molecular mechanisms regulating Snai2 expression, abundance and activity. In addition, we outline how these mechanisms contribute to disease phenotypes or how they may impact rational therapeutic targeting of Snai2 dysregulation in human disease.


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