Background： Appropriate expression and regulation of the transcriptome, which mainly comprise ofmRNAs and lncRNAs, are important for all biological and cellular processes including the physiological activities of bon...Background： Appropriate expression and regulation of the transcriptome, which mainly comprise ofmRNAs and lncRNAs, are important for all biological and cellular processes including the physiological activities of bone microvascular endothelial cells （BMECs）. Through an intricate intraeellular signaling systems, the transcriptome regulates the pharmacological response of the cells. Although studies have elucidated the impact of glucocorticoids （GCs） cell-specific gene expression signatures, it remains necessary to comprehensively characterize the impact of lncRNAs to transcriptional changes. Methods： BMECs were divided into two groups. One was treated with GCs and the other left untreated as a paired control. Differential expression was analyzed with GeneSpring software V12.0 （Agilent, Santa Clara, CA, USA） and hierarchical clustering was conducted using Cluster 3,0 software. The Gene Ontology （GO） analysis was performed with Molecular Annotation System provided by CapitalBio Corporation. Results： Our results highlight the involvement of genes implicated in development, differentiation and apoptosis following GC stimulation. Elucidation of differential gene expression emphasizes the importance of regulatory gene networks induced by GCs. We identified 73 up-regulated and 166 down-regulated long noncoding RNAs, the expression of 107 of which significantly correlated with 172 mRNAs induced by hydrocortisone. Conclusions： Transcriptome analysis of BMECs from human samples was performed to identify specific gene networks induced by GCs. Our results identified complex RNA crosstalk underlying the pathogenesis of steroid-induced necrosis of femoral head.展开更多
Testis specific protein Y-encoded（TSPY） is a Y-located proto-oncogene predominantly expressed in normal male germ cells and various types of germ cell tumor. Significantly, TSPY is frequently expressed in somatic ca...Testis specific protein Y-encoded（TSPY） is a Y-located proto-oncogene predominantly expressed in normal male germ cells and various types of germ cell tumor. Significantly, TSPY is frequently expressed in somatic cancers including liver cancer but not in adjacent normal tissues, suggesting that ectopic TSPY expression could be associated with oncogenesis in non-germ cell cancers. Various studies demonstrated that TSPY expression promotes growth and proliferation in cancer cells; however, its relationship to other oncogenic events in TSPY-positive cancers remains unknown. The present study seeks to correlate TSPY expression with other molecular features in clinical cancer samples, by analyses of RNA-seq transcriptome and DNA methylation data in the Cancer Genome Atlas（TCGA） database. A total of 53 genes,including oncogenic lineage protein 28 homolog B（LIN28B） gene and RNA-binding motif protein Y-linked（RBMY） gene, are identified to be consistently co-expressed with TSPY, and have been collectively designated as the TSPY co-expression network（TCN）. TCN genes were simultaneously activated in subsets of liver hepatocellular carcinoma（30%） and lung adenocarcinoma（10%） regardless of pathological stage, but only minimally in other cancer types. Further analysis revealed that the DNA methylation level was globally lower in the TCN-active than TCN-silent cancers. The specific expression and methylation patterns of TCN genes suggest that they could be useful as biomarkers for the diagnosis,prognosis and clinical management of cancers, especially those for liver and lung cancers, associated with TSPY co-expression network genes.展开更多
基金Source of Support： This work was funded by a grant from National Natural Science Foundation of China （No. 81273972）. Conflict of Interest： None declared.
文摘Background： Appropriate expression and regulation of the transcriptome, which mainly comprise ofmRNAs and lncRNAs, are important for all biological and cellular processes including the physiological activities of bone microvascular endothelial cells （BMECs）. Through an intricate intraeellular signaling systems, the transcriptome regulates the pharmacological response of the cells. Although studies have elucidated the impact of glucocorticoids （GCs） cell-specific gene expression signatures, it remains necessary to comprehensively characterize the impact of lncRNAs to transcriptional changes. Methods： BMECs were divided into two groups. One was treated with GCs and the other left untreated as a paired control. Differential expression was analyzed with GeneSpring software V12.0 （Agilent, Santa Clara, CA, USA） and hierarchical clustering was conducted using Cluster 3,0 software. The Gene Ontology （GO） analysis was performed with Molecular Annotation System provided by CapitalBio Corporation. Results： Our results highlight the involvement of genes implicated in development, differentiation and apoptosis following GC stimulation. Elucidation of differential gene expression emphasizes the importance of regulatory gene networks induced by GCs. We identified 73 up-regulated and 166 down-regulated long noncoding RNAs, the expression of 107 of which significantly correlated with 172 mRNAs induced by hydrocortisone. Conclusions： Transcriptome analysis of BMECs from human samples was performed to identify specific gene networks induced by GCs. Our results identified complex RNA crosstalk underlying the pathogenesis of steroid-induced necrosis of femoral head.
基金partially supported by a Merit-Reviewed grant from the Department of Veterans Affairsa Peer-Reviewed Cancer Research Program grant from the Department of Defense (W81XWH-16-1-0488) to Y-FCL
文摘Testis specific protein Y-encoded（TSPY） is a Y-located proto-oncogene predominantly expressed in normal male germ cells and various types of germ cell tumor. Significantly, TSPY is frequently expressed in somatic cancers including liver cancer but not in adjacent normal tissues, suggesting that ectopic TSPY expression could be associated with oncogenesis in non-germ cell cancers. Various studies demonstrated that TSPY expression promotes growth and proliferation in cancer cells; however, its relationship to other oncogenic events in TSPY-positive cancers remains unknown. The present study seeks to correlate TSPY expression with other molecular features in clinical cancer samples, by analyses of RNA-seq transcriptome and DNA methylation data in the Cancer Genome Atlas（TCGA） database. A total of 53 genes,including oncogenic lineage protein 28 homolog B（LIN28B） gene and RNA-binding motif protein Y-linked（RBMY） gene, are identified to be consistently co-expressed with TSPY, and have been collectively designated as the TSPY co-expression network（TCN）. TCN genes were simultaneously activated in subsets of liver hepatocellular carcinoma（30%） and lung adenocarcinoma（10%） regardless of pathological stage, but only minimally in other cancer types. Further analysis revealed that the DNA methylation level was globally lower in the TCN-active than TCN-silent cancers. The specific expression and methylation patterns of TCN genes suggest that they could be useful as biomarkers for the diagnosis,prognosis and clinical management of cancers, especially those for liver and lung cancers, associated with TSPY co-expression network genes.
