scholarly journals MicroRNA expression signature and target prediction in familial and sporadic primary macronodular adrenal hyperplasia (PMAH)

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Xiao-Gang Tan ◽  
Jie Zhu ◽  
Liang Cui
Keyword(s):  
Pathway Analysis ◽  
High Reliability ◽  
Target Prediction ◽  
Microrna Expression ◽  
Differentially Expressed ◽  
Adrenal Hyperplasia ◽  
Tissue Samples ◽  
Mirna Array ◽  
Functional Studies ◽  
Qrt Pcr

Abstract Background Primary macronodular adrenal hyperplasia (PMAH), previously termed ACTH-independent macronodular adrenal hyperplasia (AIMAH), is a rare cause of Cushing’s syndrome usually characterized by functioning adrenal macronodules and increased cortisol production. Methods To screen and analyse the microRNA (miRNA) profile of PMAH in order to elucidate its possible pathogenesis, a miRNA microarray was used to test tissue samples from patients with familial PMAH, patients with sporadic PMAH and normal control samples of other nontumour adrenocortical tissues and identify characteristic microRNA expression signatures. Randomly selected miRNAs were validated by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Furthermore, the key signalling pathways and miRNAs involved in PMAH pathogenesis were determined by gene ontology and pathway analysis. Results Characteristic microRNA expression signatures were identified for patients with familial PMAH (16 differentially expressed microRNAs) and patients with sporadic PMAH (8 differentially expressed microRNAs). The expression of the selected miRNAs was confirmed by qRT-PCR, suggesting the high reliability of the miRNA array analysis results. Pathway analysis showed that the most enriched pathway was the renal cell carcinoma pathway. Overexpression of miR-17, miR-20a and miR-130b may inhibit glucocorticoid-induced apoptosis in PMAH pathogenesis. Conclusion We identified the miRNA signatures in patients with familial and sporadic PMAH. The differentially expressed miRNAs may be involved in the mechanisms of PMAH pathogenesis. Specific miRNAs, such as miR-17, miR-20a and miR-130b, may be new targets for further functional studies of PMAH.

scholarly journals MicroRNA Expression Signature and Target Prediction in Familial and Sporadic ACTH-Independent Macronodular Adrenal Hyperplasia

2020 ◽  
Author(s):  
Tan Xiaogang ◽  
Jie Zhu ◽  
Cui Liang
Keyword(s):  
Pathway Analysis ◽  
High Reliability ◽  
Target Prediction ◽  
Microrna Expression ◽  
Differentially Expressed ◽  
Signal Pathways ◽  
Adrenal Hyperplasia ◽  
Rt Pcr ◽  
Tissue Samples ◽  
Mirna Array

Abstract Background: ACTH independent macronodular adrenal hyperplasia (AIMAH) is a rare disorder characterized by bilateral macronodular hyperplasia of the adrenal glands and increased cortisol production with subclinical or overt Cushing's syndrome. To screen and analyze the microRNA profile of AIMAH, so as to elucidate the possible pathogenesis of the disease. Methods: MiRNA microarray was used to test the tissue samples from familial AIMAH patients, sporadic AIMAH patients and normal controls of other non-tumor adrenocortical tissues, to identify characteristic microRNAs expression signatures. Some miRNAs were validated by RT-PCR. Furthermore, the key signal pathways and miRNAs involved in AIMAH pathogenesis were analyzed by gene ontology and pathway analysis.Results: Characteristic microRNA expression signatures were identified for familial AIMAH patients including 16 differentially expressed microRNAs and sporadic AIMAH patients including 8 differentially expressed microRNAs respectively. RT-PCR assay confirmed the chosed miRNAs expression, suggesting the high reliability of miRNA array. Pathway analysis showed that the most enriched pathway was renal cell carcinoma pathway. Overexpression of miR-17，miR-20a and miR-130b can inhibit glucocorticoid-induced apoptosis in the AIMAH pathogenesis.Conclusion: We have identified the miRNA signature in in Familial and Sporadic AIMAH patients, The differentially expressed miRNAs may be involved in the mechanisms of AIMAH pathogenesis. Specific miRNAs, such as miR-17，miR-20a and miR-130b may be new potential targets for further functional studies of AIMAH.

scholarly journals MicroRNA Expression Signature and Target Prediction in Familial and Sporadic Primary macronodular adrenal hyperplasia

2020 ◽  
Author(s):  
Tan Xiaogang ◽  
Jie Zhu ◽  
Cui Liang
Keyword(s):  
Pathway Analysis ◽  
High Reliability ◽  
Target Prediction ◽  
Microrna Expression ◽  
Differentially Expressed ◽  
Signal Pathways ◽  
Adrenal Hyperplasia ◽  
Rt Pcr ◽  
Tissue Samples ◽  
Mirna Array

Abstract Background: Primary macronodular adrenal hyperplasia (PMAH) is a rare cause of Cushing's syndrome, usually characterized by functioning adrenal macronodules and increased cortisol production.Methods: To screen and analyze the microRNA profile of PMAH, so as to elucidate the possible pathogenesis of the disease, MiRNA microarray was used to test the tissue samples from familial patients with PMAH , sporadic patients with PMAH and normal controls of other non-tumor adrenocortical tissues, to identify characteristic microRNAs expression signatures. Random selected miRNAs were validated by RT-PCR. Furthermore, the key signal pathways and miRNAs involved in PMAH pathogenesis were analyzed by gene ontology and pathway analysis.Results: Characteristic microRNA expression signatures were identified for familial patients with PMAH including 16 differentially expressed microRNAs and sporadic patients with PMAH including 8 differentially expressed microRNAs respectively. RT-PCR assay confirmed the chosed miRNAs expression, suggesting the high reliability of miRNA array. Pathway analysis showed that the most enriched pathway was renal cell carcinoma pathway. Overexpression of miR-17，miR-20a and miR-130b may be inhibit glucocorticoid-induced apoptosis in the PMAH pathogenesis.Conclusion: We have identified the miRNA signature in in Familial and Sporadic patients with PMAH, The differentially expressed miRNAs may be involved in the mechanisms of PMAH pathogenesis. Specific miRNAs, such as miR-17，miR-20a and miR-130b may be new potential targets for further functional studies of PMAH.

scholarly journals miRNA Expression Characterizes Histological Subtypes and Metastasis in Penile Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1480
Author(s):  
Hiresh Ayoubian ◽  
Joana Heinzelmann ◽  
Sebastian Hölters ◽  
Oybek Khalmurzaev ◽  
Alexey Pryalukhin ◽  
...  
Keyword(s):  
Microarray Data ◽  
Expression Patterns ◽  
Hpv Infection ◽  
Differentially Expressed ◽  
Histological Subtypes ◽  
Specific Expression ◽  
Tissue Samples ◽  
Qrt Pcr ◽  
Differentially Expressed Mirnas ◽  
The Impact

Although microRNAs are described as promising biomarkers in many tumor types, little is known about their role in PSCC. Thus, we attempted to identify miRNAs involved in tumor development and metastasis in distinct histological subtypes considering the impact of HPV infection. In a first step, microarray analyses were performed on RNA from formalin-fixed, paraffin-embedded tumor (22), and normal (8) tissue samples. Microarray data were validated for selected miRNAs by qRT-PCR on an enlarged cohort, including 27 tumor and 18 normal tissues. We found 876 significantly differentially expressed miRNAs (p ≤ 0.01) between HPV-positive and HPV-negative tumor samples by microarray analysis. Although no significant differences were detected between normal and tumor tissue in the whole cohort, specific expression patterns occurred in distinct histological subtypes, such as HPV-negative usual PSCC (95 differentially expressed miRNAs, p ≤ 0.05) and HPV-positive basaloid/warty subtypes (247 differentially expressed miRNAs, p ≤ 0.05). Selected miRNAs were confirmed by qRT-PCR. Furthermore, microarray data revealed 118 miRNAs (p ≤ 0.01) that were significantly differentially expressed in metastatic versus non-metastatic usual PSCC. The lower expression levels for miR-137 and miR-328-3p in metastatic usual PSCC were validated by qRT-PCR. The results of this study confirmed that specific miRNAs could serve as potential diagnostic and prognostic markers in single PSCC subtypes and are associated with HPV-dependent pathways.

Global microarray profiling identifiedhsa_circ_0064428as a potential immune-associated prognosis biomarker for hepatocellular carcinoma

2018 ◽  
Vol 56 (1) ◽  
pp. 32-38 ◽  
Author(s):  
Qiaoyou Weng ◽  
Minjiang Chen ◽  
Maoquan Li ◽  
Yong-Fa Zheng ◽  
Guoliang Shao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumour Size ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Tissue Samples ◽  
Qrt Pcr ◽  
Immunohistochemistry Staining ◽  
Microarray Profiling ◽  
Spss Software ◽  
Infiltrating Lymphocytes

BackgroundIncreasing evidence has shown that circular RNAs (circRNAs) are involved tumourigenesis and metastasis of hepatocellular carcinoma (HCC); however, progression about its function in HCC is relatively slow. Here, we aimed to investigate whether plasma circRNAs could reflect the tumour-infiltrating lymphocytes (TILs) in HCC tumour tissues and serve as prognosis biomarker for HCC.MethodsTissue samples of patients with HCC were subjected to immunohistochemistry staining against CD8 to examine the TILs. Then, we investigated the expression profile of circRNAs by microarray between plasma of patients with HCC with high TILs and low TILs, and the differentially expressed circRNAs were validated with qRT-PCR. Statistical analysis was performed with SPSS software and GraphPad Prism.ResultsWe have demonstrated that patients with HCC with high TILs exhibit a significant better overall survival, suggesting clinical outcome could be predicted by TILs. Global circRNA microarray between plasma of patients with HCC with high TILs and low TILs successfully identified six differentially expressed novel circRNAs. Among them, the expression ofhsa_circ_0064428was significantly reduced in patients with HCC with high TILs but increased in patients with low TILs. Moreover,hsa_circ_0064428was negatively correlated with patient’s survival, tumour size and metastasis.ConclusionThese findings together imply thathsa_circ_0064428could be considered as a potential HCC prognosis biomarker. Future in-depth research is required to further illustrate the involvement ofhsa_circ_0064428in HCC tumourigenesis and metastasis.

scholarly journals Bioinformatic Analysis of Circular RNA-Associated ceRNA Network Associated with Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Jiacheng Wu ◽  
Shui Liu ◽  
Yien Xiang ◽  
Xianzhi Qu ◽  
Yingjun Xie ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Pathway Analysis ◽  
Target Genes ◽  
Kegg Pathway ◽  
Interaction Network ◽  
Bioinformatic Analysis ◽  
Differentially Expressed ◽  
Qrt Pcr ◽  
Cerna Network ◽  
Kegg Pathway Analysis

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and is associated with a high mortality rate and poor treatment efficacy. In an attempt to investigate the mechanisms involved in the pathogenesis of HCC, bioinformatic analysis and validation by qRT-PCR were performed. Three circRNA GEO datasets and one miRNA GEO dataset were selected for this purpose. Upon combined biological prediction, a total of 11 differentially expressed circRNAs, 15 differentially expressed miRNAs, and 560 target genes were screened to construct a circRNA-related ceRNA network. GO analysis and KEGG pathway analysis were performed for the 560 target genes. To further screen key genes, a protein-protein interaction network of the target genes was constructed using STRING, and the genes and modules with higher degree were identified by MCODE and CytoHubba plugins of Cytoscape. Subsequently, a module was screened out and subjected to GO enrichment analysis and KEGG pathway analysis. This module included eight genes, which were further screened using TCGA. Finally, UBE2L3 was selected as a key gene and the hsa_circ_0009910–miR-1261–UBE2L3 regulatory axis was established. The relative expression of the regulatory axis members was confirmed by qRT-PCR in 30 pairs of samples, including HCC tissues and adjacent nontumor tissues. The results suggested that hsa_circ_0009910, which was upregulated in HCC tissues, participates in the pathogenesis of HCC by acting as a sponge of miR-1261 to regulate the expression of UBE2L3. Overall, this study provides support for the possible mechanisms of progression in HCC.

scholarly journals Aberrant Expression Profile of Long Noncoding RNA in Human Sinonasal Squamous Cell Carcinoma by Microarray Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Ling-zhao Meng ◽  
Ju-gao Fang ◽  
Jing-wu Sun ◽  
Fan Yang ◽  
Yong-xiang Wei
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Pathway Analysis ◽  
Expression Profile ◽  
Squamous Cell ◽  
Noncoding Rna ◽  
Differentially Expressed ◽  
Aberrant Expression ◽  
Qrt Pcr ◽  
Signal Network

Objectives. This study aimed to identify aberrantly expressed long noncoding RNAs (lncRNAs) profile of sinonasal squamous cell carcinoma (SSCC) and explore their potential functions. Methods. We investigated lncRNA and mRNA expression in SSCC and paired adjacent noncancerous tissues obtained from 6 patients with microarrays. Gene ontology (GO) analysis and pathway analysis were utilized to investigate the gene function. Gene signal-network and lncRNA-mRNA network were depicted. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to validate 5 lncRNAs in a second set of paired SSCC and adjacent noncancerous tissues obtained from 22 additional patients. Results. We identified significantly differentially expressed lncRNAs (n=3146) and mRNAs (n=2208) in SSCC relative to noncancerous tissues. The GO annotation indicated that there are some core gene products that may be attributed to the progress of SSCC. The pathway analysis identified many pathways associated with cancer. The results of lncRNA-mRNA network and gene signal-network implied some core lncRNAs/mRNAs might play important roles in SSCC pathogenesis. The results of qRT-PCR showed that all of the 5 lncRNAs were differentially expressed and consistent with the microarray results. Conclusion. Our study is the first screening and analysis of lncRNAs expression profile in SSCC and may offer new insights into pathogenesis of this disease.

Involvement of miRNAs in the formation and maintenance of self-renewing kidney cancer spheres with stem cell properties.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 463-463
Author(s):  
Zsuzsanna Lichner ◽  
Carol Saleh ◽  
Venkateshwaran Subramaniam ◽  
Gerard Prud'homme ◽  
George M. Yousef
Keyword(s):  
Stem Cell ◽  
Mirna Expression ◽  
Epithelial Mesenchymal Transition ◽  
Target Prediction ◽  
Tumor Model ◽  
Defined Medium ◽  
Differentially Expressed ◽  
Mesenchymal Transition ◽  
Immunodeficient Mice ◽  
Qrt Pcr

463 Background: Cancer cells may acquire stem cell (CSC) properties by activated TGFβ-epithelial-mesenchymal transition (EMT) axis resulting in formation of cancer stem cells. miRNAs are involved in CSC formation in solid tumors, but their role has not been investigated in renal cell carcinoma (RCC). Methods: RCC spheres were generated and propagated in serum-free defined medium (SFDM). mRNA expression was assessed by qRT-PCR. miRNA expression was screened on a qRT-PCR based panel. Tumorigenicity was assessed by subcutaneous injection of RCC sphere or parental cells into immunodeficient mice in different dilutions. TargetScan and miRPath was used for target prediction and clustering. Results: We isolated self-renewing cancer spheres from ACHN and CAKI-1 RCC cell lines in the stem cell supporting media, SFDM. Spheres were highly clonogenic and tumorigenic in xenograft tumor model and expressed high levels of stem cell-related markers and mesenchymal markers. These spheres were enriched in the mesenchymal marker CD44 and the kidney progenitor maker CD24 indicating that EMT contributed to their formation or maintenance. We compared miRNA expression between the spheres and the parental cells and identified differentially expressed miRNAs. Functional clustering of their predicted targets indicates that TGFβ signaling is a potential regulator of CSC self-renewal and is regulated by the candidate miRNAs. Further, we show that transfection of ACHN and CAKI-1 cells with the miR-17 inhibitor resulted in rapid and highly efficient formation of cancer spheres that were indistinguishable from the spheres formed in SFDM. These spheres were stable and could be propagated indefinitely. Histologic examination and immunohistochemistry of the sphere-derived xenografts confirmed the presence of clear cell RCC with large areas of sarcomatoid dedifferentiation. Finally, we prove that the TGFβ receptor II, and the co-Smad Smad4 are possible direct targets of miR-17. Conclusions: The TGFβ-EMT axis likely contributes to the self-renewing potential of RCC spheres. miRNAs are differentially expressed in RCC spheres and miR-17 inhibition transformed ccRCC cells to highly tumorigenic RCC spheres.

scholarly journals Pathway Analysis of Differentially Expressed Genes in Patients with Acute Aortic Dissection

2009 ◽  
Vol 4 ◽  
pp. BMI.S2530 ◽  
Author(s):  
Salah A. Mohamed ◽  
Hans H. Sievers ◽  
Thorsten Hanke ◽  
Doreen Richardt ◽  
Claudia Schmidtke ◽  
...  
Keyword(s):  
Aortic Dissection ◽  
Differentially Expressed Genes ◽  
Pathway Analysis ◽  
Acute Aortic Dissection ◽  
Differentially Expressed ◽  
Control Group ◽  
Pathophysiological Mechanism ◽  
Qrt Pcr ◽  
Starting Point ◽  
Fibrillin 1

Background Acute aortic dissection (AAD) is a life-threatening condition with high mortality and a relatively unclarified pathophysiological mechanism. Although differentially expressed genes in AAD have been recognized, interactions between these genes remain poorly defined. This study was conducted to gain a better understanding of the molecular mechanisms underlying AAD and to support the future development of a clinical test for monitoring patients at high risk. Materials and Methods Aortic tissue was collected from 19 patients with AAD (mean age 61.7 ± 13.1 years), and from eight other patients (mean age 32.9 ± 12.2 years) who carried the mutated gene for Marfan syndrome (MS). Six patients (mean age 56.7 ± 12.3 years) served as the control group. The PIQOR™ Immunology microarray with 1076 probes in quadruplicates was utilized; the differentially expressed genes were analysed in a MedScan search using PathwayAssist software. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and protein analysis were performed. Results Interactions of MS fibrillin-1 (FBN1) in the MedScan pathway analysis showed four genes, fibulin-1 (FBLN1), fibulin-2 (FBLN2), decorin (DCN) and microfibrillar associated protein 5 (MFAP5), which were differentially expressed in all tissue from AAD. The validation of these genes by qRT-PCR revealed a minimum of three-fold downregulation of FBLN1 (0.5 ± 0.4 vs. 6.1 ± 2.3 fold, p = 0.003) and of DCN (2.5 ± 1.0 vs. 8.5 ± 4.7 fold, p = 0.04) in AAD compared to MS and control samples. Conclusions Downregulation of fibrillin-1 (FBN1) may weaken extracellular components in the aorta and/or interfer with the transmission of cellular signals and eventually cause AAD. Additional research on these four identified genes can be a starting point to develop a diagnostic tool.

scholarly journals Microarray Expression Profile of Circular RNAs in Plasma from Primary Biliary Cholangitis Patients

2017 ◽  
Vol 44 (4) ◽  
pp. 1271-1281 ◽  
Author(s):  
Jiajia Zheng ◽  
Zhenrong Li ◽  
Tiancheng Wang ◽  
Yang Zhao ◽  
Yongfeng Wang
Keyword(s):  
Expression Profile ◽  
Expression Profiles ◽  
Characteristic Curve ◽  
Group Versus ◽  
Target Prediction ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Primary Biliary Cholangitis ◽  
Healthy Controls ◽  
Qrt Pcr

Background/Aims: Circular RNAs (circRNAs) play a crucial role in the occurrence of several diseases, including autoimmune diseases. However, their role in primary biliary cholangitis (PBC) remains unclear. Here, we aimed to determine the circRNA expression profile in plasma from PBC patients and further explore the value of circRNA in diagnosing PBC. Methods: CircRNA microarrays were used to determine circRNA expression profiles in plasma samples from 6 PBC patients and 6 healthy controls. Statistical analyses identified differentially expressed circRNAs, and these circRNAs were verified by qRT-PCR in 29 PBC patients and 30 healthy controls. MicroRNA (miRNA) target prediction software identified putative miRNA response elements (MREs), which were used to construct a map of circRNA-miRNA interactions for the differentially expressed circRNAs. Results: Our results indicated that there were 18 up-regulated and 4 down-regulated circular RNAs in the plasma from PBC patients compared with that from healthy individuals. Among the differentially expressed circRNAs, hsa_circ_402458 (P=0.0033), hsa_circ_087631 and hsa_circ_406329 (P=0.0185) were up-regulated, and hsa_circ_407176 (P=0.0066) and hsa_circ_082319 were down-regulated in the PBC group versus the healthy group as demonstrated by qRT-PCR. In particular, hsa_circ_402458 was significantly higher in PBC patients not receiving UDCA treatment than in PBC patients receiving UDCA treatment (P=0.0338). The area under the receiver operating characteristic curve for hsa_circ_402458 for diagnosing PBC was 0.710 (P=0.005). For hsa_circ_402458, two putative miRNA targets, hsa-miR-522-3p and hsa-miR-943, were predicted. Conclusions: circRNA dysregulation may play a role in PBC pathogenesis, and hsa_circ_402458 shows promise as a candidate biomarker for PBC.

scholarly journals Screening differentially expressed genes of pancreatic cancer between Mongolian and Han people using bioinformatics technology

2019 ◽  
Author(s):  
Jiasheng Xu ◽  
Kaili Liao ◽  
ZHONGHUA FU ◽  
ZHENFANG XIONG
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Gene Ontology ◽  
Differentially Expressed Genes ◽  
Pathway Analysis ◽  
Differentially Expressed ◽  
Cancer Tissue ◽  
Pancreatic Cancer Tissue ◽  
Tissue Samples ◽  
Multiple Difference

Abstract Objective To screen and analyze differentially expressed genes in pancreatic carcinoma tissues taken from Mongolian and Han patients by Affymetrix Genechip. Methods: Pancreatic ductal cell carcinoma tissues were collected from the Mongolian and Han patients undergoing resection in the Second Affiliated Hospital of Nanchang University during March 2015 to May 2018 and the total RNA was extracted. Differentially expressed genes were selected from the total RNA qualified by Nanodrop 2000 and Agilent 2100 using Affymetrix and a cartogram was drawn; The gene ontology (GO) analysis and Pathway analysis were used for the collection and analysis of biological information of these differentially expressed genes. Finally, some differentially expressed genes were verified by real-time PCR. Results Through the microarray analysis of gene expression, 970 differentially expressed genes were detected by comparing pancreatic cancer tissue samples between Mongolian and Han patients. A total of 257 genes were significantly up-regulated in pancreatic cancer tissue samples in Mongolian patients;while a total of 713 genes were down-regulated. In the Gene Ontology database, 815 differentially expressed genes were identified with clear GO classification, and CPB1 gene had the highest multiple of differential expression (difference multiple: 31.76). The Pathway analysis detected 28 signaling pathways that included these differentially expressed genes, involving a total of 178 genes. Among these pathways, the enrichment of differentially expressed genes in the FAK signaling pathway was the highest and COL11A1 gene had the highest multiple difference (multiple difference: 5.02). The expressions of differentially expressed genes CPB1, COL11A1、ITGA4、BIRC3、PAK4、CPA1、CLPS、PIK3CG and HLA-DPA1 determined by real-time PCR were consistent with the results of gene chip analysis. Conclusions The results of microarray analysis of gene expression profiles showed that there are a large number of differentially expressed genes in pancreatic cancer tissue samples compared between Mongolian and Han populations. These genes are closely related to the proliferation, differentiation, invasion and metastasis and multi-drug resistance of pancreatic cancer and are involved in the regulation of multiple important signaling pathways in organisms.

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