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microarray analysis of long-noncoding RNAs and mRNA expression profiles in human steroid-induced avascular necrosis of the femoral head

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JOURNAL OF CELLULAR BIOCHEMISTRY 2019年第9期120卷 15800-15813页

作者： Luo, Hongbin Lan, Weibin Li, Yongfeng Lian, Xiaolan Zhang, Nanwen Lin, Xinhua Chen, Peng Fujian Med Univ Affiliated Hosp 1 Dept Joint Surg & Sports Med Fuzhou Fujian Peoples R China Fujian Med Univ Sch Pharm Fuzhou Fujian Peoples R China Fujian Med Univ Longyan Hosp 1 Dept Orthoped Longyan Peoples R China Fujian Med Univ Sch Clin Med 1 Fuzhou Fujian Peoples R China Fujian Med Univ Union Hosp Fujian Prov Key Lab Hematol Fujian Inst Hematol Fuzhou Fujian Peoples R China

This study performed the first microarray analysis of long-noncoding RNA (lncRNA) and mRNA expression profiles in human steroid-induced avascular necrosis of the femoral head (SAVNFH). expression levels of lncRNAs and mRNAs in three human SAVNFH samples and three human femoral head fracture samples (controls) were detected using third-generation lncRNA microarrays (KangChen Biotech, Shanghai, China). The fold change, false discovery rate, and P value were utilized to filter genes with significant differential expression in the SAVNFH samples compared with the control samples. In total, there were 1179 upregulated and 3214 downregulated lncRNAs (P2. zerofold, P < 0.05). Meanwhile, 1092 upregulated and 565 downregulated mRNAs were found in the SAVNFH samples compared with the control samples. Then, quantitative real-time polymerase chain reaction was used to confirm the previous microarray results using 8 and 20 selected dysregulated lncRNAs and mRNAs, respectively, and the results generally confirmed the microarray findings. Finally, we used Gene Ontology (GO) and pathway analysis to investigate the functions of the altered mRNAs and their associated GO terms and biological pathways. The Immune system process term (GO:0002376) was the most significantly upregulated GO term, and the Regulation of blood coagulation term (GO:0030193) was the most significantly downregulated GO term in the biological process category for the SAVNFH samples. "Hematopoietic cell lineage - Homo sapiens (human) (Pathway ID: hsa04640)" and "Complement and coagulation cascades - Homo sapiens (human) (Pathway ID: hsa04610)" were the most significantly up- and downregulated pathways in the SAVNFH samples compared with the controls. In conclusion, the differential expression of lncRNAs and mRNAs may be correlated with the pathogenesis of SAVNFH, and these significantly dysregulated lncRNAs and mRNAs may function through networks or participate in several specific biological processes. Further res

关键词： long-noncoding RNAs microarray expression mRNAs steroid-induced avascular necrosis of the femoral head

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The Influence of Salinomycin on the expression Profile of mRNAs Encoding Selected Caspases and MiRNAs Regulating their expression in Endometrial Cancer Cell Line

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CURRENT PHARMACEUTICAL BIOTECHNOLOGY 2020年第14期21卷 1505-1515页

作者： Januszyk, Krzysztof Januszyk, Piotr Grabarek, Beniamin O. Boron, Dariusz Oplawski, Marcin Publ Higher Med Profess Sch Opole Fac Hlth Sci Opole Poland Ludwik Rydygier Mem Specialized Hosp Dept Gynecol & Obstet Gynecol Oncol Krakow Poland Maria Sklodowska Curie Natl Res Inst Oncol Krakow Krakow Poland Univ Technol Fac Med Dept Histol Cytophysiol & Embryol Zabrze Poland

Background: Apoptosis could take place in the pathway dependent on death receptors or pathways dependent on mitochondria. In both, a key role is played by enzymes with protease activity, known as caspases. Aim: The aim of this study was to assess the variances in the expression pattern of caspase-dependent signaling pathways in the endometrial cancer cell line when treated with salinomycin. Additionally, the changes in the level of miRNA that potentially regulate these mRNAs were evaluated. Materials and Methods: Endometrial cancer cells were treated with 1 mu M of salinomycin for 12, 24 and 48 hours. Untreated cells made up the control culture. The molecular analysis consisted of screening mRNA and miRNA microarray expression profiles of caspases, and the evaluation of the expression of caspases 3,8 and 9 by RTqPCR, also on the protein level. Results and Discussion: It was observed that 5 of the 14 differentiating mRNAs were commonly found for all incubation times of the cells and they corresponded with CASP3, CASP8, and CASP9 genes. The highest impact probability was determined between CASP3(up-regulated) and hsa- miR-30d (FC -2.01), CASP8 (down-regulated) and hsa-miR-21 (FC +1.39) and between CASP9 (upregulated) and hsa-miR-1271 (FC +1.71). Conclusion: Salinomycin induces the apoptosis of endometrial cancer cells. The largest increase in activity was noted for caspases 3 and 9, while the expression of caspase 8 was decreased. Salinomycin causes a regulatory effect on the transcriptomes of mRNA and miRNA in in vitro endometrial cancer cells.

关键词： Mitochondria-dependent independent apoptosis pathway salinomycin endometrial cancer miRNA mRNA microarray expression

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Construction and comprehensive analysis of a ceRNA network to reveal potential prognostic biomarkers for lung adenocarcinoma

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BMC CANCER 2021年第1期21卷 849-849页

作者： Gao, Lei Zhang, Ling Anhui Med Univ Dept Resp & Crit Care Med Hosp 2 Econ & Technol Dev Zone 678 Furong Rd Hefei 230601 Anhui Peoples R China Anhui Med Univ Affiliated Hosp 1 Dept Crit Care Med 218 Jixi Rd Hefei 230022 Anhui Peoples R China

Background More and more studies have proven that circular RNAs (circRNAs) play vital roles in cancer development via sponging miRNAs. However, the expression pattern of competing endogenous RNA (ceRNA) in lung adenocarcinoma (LUAD) remains largely unclear. The current study explored functional roles and the regulatory mechanisms of circRNA as ceRNAs in LUAD and their potential impact on LUAD patient prognosis. Methods In this study, we systematically screened differential expression circRNAs (DEcircRNAs), miRNAs (DEmiRNAs) and mRNAs (DEGs) associated with LUAD. Then, DEcircRNAs, DEmiRNAs and DEGs were selected to construct a circRNA-miRNA-mRNA prognosis-related regulatory network based on interaction information from the ENCORI database. Subsequently, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the genes in the network to predict the potential underlying mechanisms and functions of circRNAs in LUAD. In addition, Kaplan-Meier survival analysis was performed to evaluate clinical outcomes of LUAD patients, and drug sensitivity analysis was used to screen potential biomarkers for drug treatment of patients with LUAD. Results As a result, 10 circRNAs were aberrantly expressed in LUAD tissues. The ceRNA network was built, which included 3 DEcircRNAs, 6 DEmiRNAs and 157 DEGs. The DEGs in the ceRNA network of hsa_circ_0049271 enriched in biological processes of cell proliferation and the Jak-STAT signaling pathway. We also detected 7 mRNAs in the ceRNA network of hsa_circ_0049271 that were significantly associated with the overall survival of LUAD patients (P < 0.05). Importantly, four genes (PDGFB, CCND2, CTF1, IL7R) identified were strongly associated with STAT3 activation and drugs sensitivity in GDSC. Conclusions In summary, a ceRNA network of hsa_circ_0049271 was successfully constructed, which including one circRNA, two miRNAs, and seven mRNAs. Seven mRNAs (PDGFB, TNFRSF19, CCND2, CTF1, IL11R

关键词： Circular RNA Lung adenocarcinoma microarray expression Competing endogenous RNA Overall survival Prognostic biomarker Drug sensitivity

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hsa_circ_0000729, a potential prognostic biomarker in lung adenocarcinoma

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THORACIC CANCER 2018年第8期9卷 924-930页

作者： Li, Shicheng Sun, Xiao Miao, Shuncheng Lu, Tong Wang, Yuanyong Liu, Jia Jiao, Wenjie Qingdao Univ Affiliated Hosp Dept Thorac Surg 16 Jiangsu Rd Qingdao 266003 Peoples R China Qingdao Univ Sch Pharm 38 Dengzhou Rd Qingdao 266003 Peoples R China

BackgroundIncreasing evidence has demonstrated that circular RNAs (circRNAs) may play an important role in oncogenesis and tumor development;however, their role in lung adenocarcinoma (LUAD) remains unclear. We identified the differentially expressed circRNAs in LUAD and investigated the potential mechanisms for cancer progression. MethodsWe examined differentially expressed circRNAs in LUAD and paired normal tissues using downloaded circRNA microarrays from the Gene expression Omnibus. We constructed gene co-expression networks based on the degree of Pearson correlation to predict the critical circRNA in LUAD. Gene Ontology analysis was performed on the genes in the network. We observed one novel circRNA upregulated in LUAD, hsa_circ_0000792, as well as its potential sponged microRNA, miR-375. Subsequent real-time quantitative PCR was used to verify the bioinformatics analysis. ResultsSeveral circRNAs showed significantly different expression levels in LUAD tissues. Real-time quantitative PCR and further co-expression network analysis of 42 matched tissue samples showed a significant difference in expression between LUAD and normal tissues in hsa_circ_0000792 (P < 0.001). We built a network of hsa_circ_0000792-targeted miRNA gene interactions, including miR-375 and the corresponding messenger RNAs. Gene Ontology analysis revealed that hsa_circ_0000792 could participate in signal transduction and cell communication during LUAD development. Larger area under the curve by receiver operating characteristic curve analysis of hsa_circ_0000792 and miR-375 (0.815 and 0.772, respectively) in LUAD indicated greater potential as biomarkers. ConclusionsWe identified hsa_circ_0000792 as a potential LUAD biomarker;however, further studies are required to determine the mechanism of this circRNA in LUAD development.

关键词： Circular RNA lung adenocarcinoma microarray expression prognostic biomarker

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The growth inhibitory effect of gambogic acid on pancreatic cancer cells

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NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY 2018年第5期391卷 551-560页

作者： Youns, Mahmoud ElKhoely, Abeer Kamel, Rehab German Canc Res Ctr Dept Funct Genome Anal Neuenheimer Feld 580 D-69120 Heidelberg Germany Oman Pharm Inst Muscat Oman Helwan Univ Dept Biochem & Mol Biol Fac Pharm Cairo Egypt Helwan Univ Dept Pharmacol & Toxicol Fac Pharm Cairo Egypt

Pancreatic cancer, the fourth most common cause of cancer-related deaths, is one of the most aggressive and devastating human malignancies with increasing incidence worldwide. To date, surgical resection is the only potentially curative therapy available for pancreatic cancer patients. Early diagnosis of pancreatic tumors is difficult, and hence, nearly 80% of patients cannot receive surgical resection. Natural products have always been a vital source for novel compounds for cancer treatment. The naturally occurring prenylated xanthone, gambogic acid, has been previously shown to exert potent anticancer, anti-inflammatory, apoptotic, antiangiogenic, and antioxidant activities. However, to our knowledge, there have been no specific studies showing its effect on the whole-genome expression in pancreatic cancer cells. Here, the anticancer activity of gambogic acid toward a panel of pancreatic cancer cells with different differentiation stages has been evaluated. Additionally, a whole-genome transcription profiling study was performed in order to identify possible candidate players modulating the antitumor effect of gambogic acid on pancreatic cancer cells. expression analysis results showed that the pancreatic adenocarcinoma signaling pathway was specifically affected upon gambogic acid treatment. Moreover, the growth inhibitory effect of gambogic acid on pancreatic cancer cells was modulated through up-regulation of DDIT3, DUSP1, and DUSP5 and down-regulation of ALDOA, TOP2A, and ATG4B. The present work is a starting point for the generation of hypotheses on significantly regulated candidate key player genes and for a detailed dissection of the potential role of each individual gene for the activity of gambogic acid on pancreatic cancer.

关键词： Gambogic acid Pancreatic cancer ALDOA Topoisomerase 2A microarray expression

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Identification of putative miRNA biomarkers in early rheumatoid arthritis by genome-wide microarray profiling: A pilot study

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GENE 2019年 720卷 144081-000页

作者： Romo-Garcia, M. F. Bastian, Y. Zapata-Zuniga, M. Macias-Segura, N. Castillo-Ortiz, J. D. Lara-Ramirez, E. E. Fernandez-Ruiz, J. C. Berlanga-Taylor, A. J. Gonzalez-Amaro, R. Ramos-Remus, C. Enciso-Moreno, J. A. Castaneda-Delgado, J. E. IMSS Unidad Invest Biomed Zacatecas Zacatecas Mexico Catedras CONACyT Unidad Invest Biomed Zacatecas I Zacatecas Mexico IMSS Hosp Rural 51 Villanueva Zacatecas Mexico Unidad Invest Enfermedades Cren Degenerat Guadalajara Jalisco Mexico Univ Autonoma Guadalajara Guadalajara Jalisco Mexico Imperial Coll London Fac Med MRC PHE Ctr Environm & Hlth Dept Epidemiol & BiostatSch Publ Hlth St Marys CampusNorfolk Pl London England Univ Autonoma San Luis Potosi Fac Med Dept Inmunol San Luis Potosi San Luis Potosi Mexico Univ Autonoma Zacatecas Fac Med Humana & Ciencias Salud Zacatecas Mexico Univ Autonoma Aguascalientes Ctr Ciencias Basicas Dept Fisiol & Farmacol Lab Neuroinmunoendocrinol Aguascalientes Aguascalientes Mexico

Despite the existing research, the etiology of rheumatoid arthritis (RA), an autoimmune disease remains poorly understood with early and accurate diagnosis difficult to achieve. MicroRNAs (miRNAs) play an important role in biological processes as modulators of transcription and translation. Previous studies have demonstrated a downregulation of several genes in' early RA stages and in addition, miRNAs may serve as early biomarkers of subclinical changes in early RA. When comparing the four groups (ANOVA P < 0.01, fold change > 4), we found 253 differentially expressed miRNAs. Of these, 97 miRNAs were identified as overexpressed in early rheumatoid arthritis. The validation of miRNA microarray expression was performed in a set by RT-qPCR and showed strong agreement with microarray expression data. The putative targets of overexpressed microRNAs in early RA were significantly enriched in apoptosis, tolerance loss and Wnt pathways. Moreover, ROC analysis showed values of AUC 0.76 and P < 0.05 for miR 361-5p, identifying this miRNA as a potential biomarker of disease. We identified specific microRNAs associated with early rheumatoid arthritis and proposed them as early biomarkers of disease. Our results provide novel insight into immune disease physiopathology and describe unreported microRNAs in RA with potential for clinical use.

关键词： Early rheumatoid arthritis Biomarker miRNA CCP microarray expression

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Genome-wide analysis of DNA methylation and their associations with long noncoding RNA/ mRNA expression in non-small-cell lung cancer

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EPIGENOMICS 2017年第2期9卷 137-153页

作者： Feng, Nannan Wang, Yu Zheng, Min Yu, Xiao Lin, Hongyan Ma, Rong-Na Shi, Oumin Zheng, Xiangqian Gao, Ming Yu, Herbert Garmire, Lana Qian, Biyun Shanghai Jiao Tong Univ Sch Med Hongqiao Int Inst Med Shanghai Tongren Hosp Shanghai 200025 Peoples R China Shanghai Jiao Tong Univ Sch Med Fac Publ Hlth Shanghai 200025 Peoples R China Tianjin Med Univ Tianjin Key Lab Canc Prevent & Therapy Canc Inst & Hosp Tianjin 300060 Peoples R China Univ Hawaii Canc Epidemiol Program Ctr Canc 701 Ilalo St Honolulu HI 96813 USA

Aim: The goal of this study is to identify differentially methylated (DM) loci associated with long noncoding RNA (lncRNA)/mRNA expression in non-small-cell lung cancer (NSCLC). Materials & methods: microarrays were used to interrogate genome-wide methylation and expression of lncRNA/mRNA in NSCLC. Results: We identified 113,644 DM loci between tumors and adjacent tissues. Among them, 26,310 DM loci were associated with 1685 differentially expressed genes, and 839 genes had significant correlations between methylation and expression, of which 26 hypermethylated loci in transcription start site 200 were correlated with low gene expression. We validated the correlations between methylation and expression in five genes (CDO1, C2orf40, SCARF1, ZFP106 and IFFO1) using pyrosequencing and quantitative polymerase chain reaction. We also found significant correlations between lncRNAs and mRNAs, and validated four of the correlations with quantitative polymerase chain reaction. Conclusion: Integrated analysis of genome-wide DNA methylation and lncRNA/mRNA expression allows us to identify new DM loci-correlated with gene expression in NSCLC.

关键词： genome-wide methylation long noncoding RNA lung cancer microarray expression

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White Blood Cell Differentials Enrich Whole Blood expression Data in the Context of Acute Cardiac Allograft Rejection

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BIOINFORMATICS AND BIOLOGY INSIGHTS 2012年第6期6卷 49-61页

作者： Shannon, Casey P. Hollander, Zsuzsanna Wilson-McManus, Janet Balshaw, Robert Ng, Raymond T. McMaster, Robert McManus, Bruce M. Keown, Paul A. Tebbutt, Scott J. NCE CECR PROOF Ctr Excellence Vancouver BC Canada Univ British Columbia Dept Stat Vancouver BC Canada Univ British Columbia Dept Comp Sci Vancouver BC Canada Univ British Columbia Dept Med Genet Vancouver BC Canada Univ British Columbia Dept Med Div Nephrol Vancouver BC Canada Univ British Columbia Dept Med Div Resp Med Vancouver BC Canada UBC James Hogg Res Ctr Vancouver BC Canada Inst Heart Lung Hlth Vancouver BC Canada

Acute cardiac allograft rejection is a serious complication of heart transplantation. Investigating molecular processes in whole blood via microarrays is a promising avenue of research in transplantation, particularly due to the non-invasive nature of blood sampling. However, whole blood is a complex tissue and the consequent heterogeneity in composition amongst samples is ignored in traditional microarray analysis. This complicates the biological interpretation of microarray data. Here we have applied a statistical deconvolution approach, cell-specific significance analysis of microarrays (csSAM), to whole blood samples from subjects either undergoing acute heart allograft rejection (AR) or not (NR). We identified eight differentially expressed probe-sets significantly correlated to monocytes (mapping to 6 genes, all down-regulated in ARs versus NRs) at a false discovery rate (FDR) <= 15%. None of the genes identified are present in a biomarker panel of acute heart rejection previously published by our group and discovered in the same data.

关键词： microarray expression cell-specific expression deconvolution heart transplantation

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Three methods for optimization of cross-laboratory and cross-platform microarray expression data

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NUCLEIC ACIDS RESEARCH 2007年第10期35卷 e72-e72页

作者： Stafford, Phillip Brun, Marcel Arizona State Univ Biodesign Inst Ctr Innovat Med Tempe AZ 85287 USA Translat Genom Res Inst Div Computat Biol Phoenix AZ USA

microarray gene expression data becomes more valuable as our confidence in the results grows. Guaranteeing data quality becomes increasingly important as microarrays are being used to diagnose and treat patients (1-4). The MAQC Quality Control Consortium, the FDA's Critical Path Initiative, NCI's caBIG and others are implementing procedures that will broadly enhance data quality. As GEO continues to grow, its usefulness is constrained by the level of correlation across experiments and general applicability. Although RNA preparation and array platform play important roles in data accuracy, pre-processing is a user-selected factor that has an enormous effect. Normalization of expression data is necessary, but the methods have specific and pronounced effects on precision, accuracy and historical correlation. As a case study, we present a microarray calibration process using normalization as the adjustable parameter. We examine the impact of eight normalizations across both Agilent and Affymetrix expression platforms on three expression readouts: (1) sensitivity and power, (2) functional/ biological interpretation and (3) feature selection and classification error. The reader is encouraged to measure their own discordant data, whether cross-laboratory, cross-platform or across any other variance source, and to use their results to tune the adjustable parameters of their laboratory to ensure increased correlation.

关键词： .data quality Feature Selection cross-platform biological interpretation microarray expression normalizations

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TCLUST: A Fast Method for Clustering Genome-Scale expression Data

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IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS 2011年第3期8卷 808-818页

作者： Dost, Banu Wu, Chunlei Su, Andrew Bafna, Vineet Univ Calif San Diego Dept Comp Sci & Engn La Jolla CA 92093 USA Novartis Res Fdn Genom Inst San Diego CA 92121 USA

Genes with a common function are often hypothesized to have correlated expression levels in mRNA expression data, motivating the development of clustering algorithms for gene expression data sets. We observe that existing approaches do not scale well for large data sets, and indeed did not converge for the data set considered here. We present a novel clustering method TCLUST that exploits coconnectedness to efficiently cluster large, sparse expression data. We compare our approach with two existing clustering methods CAST and K-means which have been previously applied to clustering of gene-expression data with good performance results. Using a number of metrics, TCLUST is shown to be superior to or at least competitive with the other methods, while being much faster. We have applied this clustering algorithm to a genome-scale gene-expression data set and used gene set enrichment analysis to discover highly significant biological clusters. (Source code for TCLUST is downloadable at http://***/similar to bdost/tclust.)

关键词： microarray expression clustering graph algorithms coconnectedness

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