scholarly journals Regulation of Corticosteroidogenic Genes by MicroRNAs

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Stacy Robertson ◽  
Louise A. Diver ◽  
Samantha Alvarez-Madrazo ◽  
Craig Livie ◽  
Ayesha Ejaz ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Hormone Secretion ◽  
Bioinformatic Analysis ◽  
Multiple Points ◽  
Microrna Regulation ◽  
Adrenal Tissue ◽  
Disease States ◽  
Aldosterone Producing Adenoma ◽  
Normal Adrenal Tissue ◽  
Corticosteroid Secretion

The loss of normal regulation of corticosteroid secretion is important in the development of cardiovascular disease. We previously showed that microRNAs regulate the terminal stages of corticosteroid biosynthesis. Here, we assess microRNA regulation across the whole corticosteroid pathway. Knockdown of microRNA using Dicer1 siRNA in H295R adrenocortical cells increased levels of CYP11A1, CYP21A1, and CYP17A1 mRNA and the secretion of cortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycorticosterone, and aldosterone. Bioinformatic analysis of genes involved in corticosteroid biosynthesis or metabolism identified many putative microRNA-binding sites, and some were selected for further study. Manipulation of individual microRNA levels demonstrated a direct effect of miR-125a-5p and miR-125b-5p on CYP11B2 and of miR-320a-3p levels on CYP11A1 and CYP17A1 mRNA. Finally, comparison of microRNA expression profiles from human aldosterone-producing adenoma and normal adrenal tissue showed levels of various microRNAs, including miR-125a-5p to be significantly different. This study demonstrates that corticosteroidogenesis is regulated at multiple points by several microRNAs and that certain of these microRNAs are differentially expressed in tumorous adrenal tissue, which may contribute to dysregulation of corticosteroid secretion. These findings provide new insights into the regulation of corticosteroid production and have implications for understanding the pathology of disease states where abnormal hormone secretion is a feature.

Bioinformatic analysis of altered microRNA production in normal adrenal tissue and aldosterone-producing adenoma

2014 ◽  
Author(s):  
Nur Izah Ab Razak ◽  
Louise Diver ◽  
Samantha Alvarez-Madrazo ◽  
Stacy Robertson ◽  
Martin McBride ◽  
...  
Keyword(s):  
Bioinformatic Analysis ◽  
Adrenal Tissue ◽  
Aldosterone Producing Adenoma ◽  
Normal Adrenal Tissue

scholarly journals Gene Expression Profiles Associated with Radio-Responsiveness in Locally Advanced Rectal Cancer

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 500
Author(s):  
Jeeyong Lee ◽  
Junhye Kwon ◽  
DaYeon Kim ◽  
Misun Park ◽  
KwangSeok Kim ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Expression Profiles ◽  
Cell Cycle Control ◽  
Methylation Status ◽  
Locally Advanced ◽  
Gene Expression Profiles ◽  
Advanced Rectal Cancer ◽  
Bioinformatic Analysis ◽  
Locally Advanced Rectal Cancer ◽  
Genes Encoding

LARC patients were sorted according to their radio-responsiveness and patient-derived organoids were established from the respective cancer tissues. Expression profiles for each group were obtained using RNA-seq. Biological and bioinformatic analysis approaches were used in deciphering genes and pathways that participate in the radio-resistance of LARC. Thirty candidate genes encoding proteins involved in radio-responsiveness–related pathways, including the immune system, DNA repair and cell-cycle control, were identified. Interestingly, one of the candidate genes, cathepsin E (CTSE), exhibited differential methylation at the promoter region that was inversely correlated with the radio-resistance of patient-derived organoids, suggesting that methylation status could contribute to radio-responsiveness. On the basis of these results, we plan to pursue development of a gene chip for diagnosing the radio-responsiveness of LARC patients, with the hope that our efforts will ultimately improve the prognosis of LARC patients.

scholarly journals Uncontrolled Diabetes Mellitus Has No Major Influence on the Platelet Transcriptome

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Thomas G. Nührenberg ◽  
Marco Cederqvist ◽  
Federico Marini ◽  
Christian Stratz ◽  
Björn A. Grüning ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Next Generation Sequencing ◽  
Platelet Reactivity ◽  
Platelet Rich Plasma ◽  
Expression Profiles ◽  
Bioinformatic Analysis ◽  
Differentially Expressed ◽  
Major Influence ◽  
Next Generation ◽  
Generation Sequencing

Background. Diabetes mellitus (DM) has been associated with increased platelet reactivity as well as increased levels of platelet RNAs in plasma. Here, we sought to evaluate whether the platelet transcriptome is altered in the presence of uncontrolled DM. Methods. Next-generation sequencing (NGS) was performed on platelet RNA for 5 patients with uncontrolled DM (HbA1c 9.0%) and 5 control patients (HbA1c 5.5%) with otherwise similar clinical characteristics. RNA was isolated from leucocyte-depleted platelet-rich plasma. Libraries of platelet RNAs were created separately for long RNAs after ribosomal depletion and for small RNAs from total RNA, followed by next-generation sequencing. Results. Platelets in both groups demonstrated RNA expression profiles characterized by absence of leukocyte-specific transcripts, high expression of well-known platelet transcripts, and in total 6,343 consistently detectable transcripts. Extensive statistical bioinformatic analysis yielded 12 genes with consistently differential expression at a lenient FDR < 0.1, thereof 8 protein-coding genes and 2 genes with known expression in platelets (MACF1 and ITGB3BP). Three of the four differentially expressed noncoding genes were YRNAs (RNY1, RNY3, and RNY4) which were all downregulated in DM. 23 miRNAs were differentially expressed between the two groups. Of the 13 miRNAs with decreased expression in the diabetic group, 8 belonged to the DLK1–DIO3 gene region on chromosome 14q32.2. Conclusions. In this study, uncontrolled DM had a remote impact on different components of the platelet transcriptome. Increased expression of MACF1, together with supporting predicted mRNA-miRNA interactions as well as reduced expression of RNYs in platelets, may reflect subclinical platelet activation in uncontrolled DM.

scholarly journals Identification of Differentially Expressed Genes and associated pathways common to Eyelid and Non-Ocular Basal Cell Carcinoma to understand the Molecular Biology of BCC

2021 ◽  
Author(s):  
Perumal Jayaraj ◽  
Seema Sen ◽  
Pranjal Vats ◽  
Shefali Dahiya ◽  
Vanshika Mohindroo
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Bioinformatic Analysis ◽  
Malignant Neoplasms ◽  
Pathway Enrichment Analysis ◽  
Hub Genes ◽  
Pathway Enrichment

Background: Eyelid BCC accounts for more than 90% of Eyelid malignant neoplasms. Various aberrant signalling pathways and genes in Non-Ocular BCC have been found whereas Eyelid bcc remains elusive. Objective: This study aims to find the common DEGs of Eyelid and Non-Ocular BCC using bioinformatic analysis and text mining to gain more insights into the molecular aspects common to both BCC non-ocular and Eyelid BCC and to identify common potential prognostic markers. Material and method: The Gene Expression profiles of Eyelid BCC (GSE103439) and Non-Ocular BCC (GSE53462) were obtained from the NCBI GEO database followed by identification of common DEGs. Protein-Protein interaction and Pathway Enrichment analysis of these screened genes was done using bioinformatic tools like STRING, Cytoscape and BiNGO, DAVID, KEGG respectively. Results: A total of 181 genes were found common in both datasets. A PPI network was formed for the screened genes and 20 HUB genes were sorted which included CTNNB1, MAPK14, BTRC, EGFR, ADAM17. Pathway enrichment of HUB genes showed that they were dysregulated in carcinogenic and apoptotic pathways that seem to play a role in the progression of both the BCC. Conclusion: The result and findings of bioinformatic analysis highlighted the molecular pathways and genes enriched in both Eyelid BCC as well as Non- Ocular BCC. The identified pathways should be studied further to recognise common molecular events that would lead to the progression of BCC. This may provide a window to explore the prognostic and therapeutic strategies common to both BCC. Keywords: Basal cell carcinoma (BCC), Cancer, Microarray, Ophthalmology, Tumour marker

scholarly journals A Preliminary Study on the Characteristics of microRNAs in Ovarian Stroma and Follicles of Chuanzhong Black Goat during Estrus

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 970
Author(s):  
Tingting Lu ◽  
Xian Zou ◽  
Guangbin Liu ◽  
Ming Deng ◽  
Baoli Sun ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Hormone Secretion ◽  
Mapk Signaling ◽  
Functional Enrichment ◽  
Small Rna Sequencing ◽  
Follicular Maturation ◽  
Ovarian Stroma

microRNAs (miRNAs) play a significant role in ovarian follicular maturity, but miRNA expression patterns in ovarian stroma (OS), large follicles (LF), and small follicles (SF) have been rarely explored. We herein aimed to identify miRNAs, their target genes and signaling pathways, as well as their interaction networks in OS, LF, and SF of Chuanzhong black goats at the estrus phase using small RNA-sequencing. We found that the miRNA expression profiles of LF and SF were more similar than those of OS—32, 16, and 29 differentially expressed miRNAs were identified in OS vs. LF, OS vs. SF, and LF vs. SF, respectively. Analyses of functional enrichment and the miRNA-targeted gene interaction network suggested that miR-182 (SMC3), miR-122 (SGO1), and miR-206 (AURKA) were involved in ovarian organogenesis and hormone secretion by oocyte meiosis. Furthermore, miR-202-5p (EREG) and miR-485-3p (FLT3) were involved in follicular maturation through the MAPK signaling pathway, and miR-2404 (BMP7 and CDKN1C) played a key role in follicular development through the TGF-β signaling pathway and cell cycle; nevertheless, further research is warranted. To our knowledge, this is the first study to investigate miRNA expression patterns in OS, LF, and SF of Chuanzhong black goats during estrus. Our findings provide a theoretical basis to elucidate the role of miRNAs in follicular maturation. These key miRNAs might provide candidate biomarkers for the diagnosis of follicular maturation and will assist in developing new therapeutic targets for female goat infertility.

Expression profiles of tRNA-derived fragments and their potential roles in ovarian endometriosis

Epigenomics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 183-197
Author(s):  
Licong Shen ◽  
Xiaxia Hong ◽  
Wenjun Zhou ◽  
Yi Zhang
Keyword(s):  
Expression Profiles ◽  
Bioinformatic Analysis ◽  
Vital Role ◽  
Small Rna Sequencing ◽  
Chain Reaction ◽  
Ovarian Endometriosis ◽  
Paired Samples ◽  
Polymerase Chain ◽  
Pathway Analyses ◽  
Ovarian Endometriomas

Aim: Transfer RNA-derived fragments have been reported to play a vital role in disease progression, but their role in the pathogenesis of endometriosis remains unknown. Materials & methods: Small RNA sequencing was conducted in three paired ovarian endometriomas and eutopic endometria. The data from 22 paired samples were validated by quantitative real-time polymerase chain reaction (qPCR) and bioinformatic analysis was performed to establish the roles of these fragments in endometriosis pathogenesis. Results: We identified 19 upregulated and five downregulated tRNA-derived fragments, of which tiRNA-5 was the most common. Gene Ontology and pathway analyses revealed that these molecules could have roles in the pathogenesis of endometriosis. Conclusion: tRNA-derived fragments are dysregulated and could be involved in the pathogenesis and progression of ovarian endometriosis.

Adrenocortical Carcinoma: Clinical, Morphologic, and Molecular Characterization

2002 ◽  
Vol 20 (4) ◽  
pp. 941-950 ◽  
Author(s):  
Alexander Stojadinovic ◽  
Ronald A. Ghossein ◽  
Axel Hoos ◽  
Aviram Nissan ◽  
David Marshall ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Cox Regression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Prognostic Significance ◽  
Phenotypic Expression ◽  
Patient Specific ◽  
Rank Test ◽  
Primary Tumors ◽  
Adrenal Tissue

PURPOSE: To define multimolecular phenotypes of adrenocortical carcinoma (ACC) and to correlate outcome with morphologic and molecular parameters. PATIENTS AND METHODS: Clinical data were analyzed for 124 patients, histopathologic slides for 67 primary tumors, and tissue specimens for 74 patients (38 primary and 36 metastatic tumors) with ACC and for 38 normal adrenal tissue samples. Molecular expression profiles were investigated by immunohistochemistry. The prognostic significance of 12 gross and histologic parameters in 67 primary ACCs was evaluated. Morphologic and protein expression patterns were correlated with disease-specific survival (DSS). Univariate influence of prognostic factors on DSS was analyzed by log-rank test and multivariate analysis by Cox regression. RESULTS: The median follow-up period was 4.7 years. Significant predictors of DSS included distant metastasis at time of initial presentation; venous, capsular, and adjacent organ invasion; tumor necrosis, mitotic rate, atypical mitosis, and mdm-2 overexpression. Five-year DSS by number (one to six) of adverse histologic parameters was as follows: one to two, 84%; three to four, 37%; more than four, 9% (P = .005).The phenotype Ki-67(−)p53(−)mdm-2(+)cyclinD1(−)Bcl-2(−)p21(−)p27(+) was observed in 83% of normal and 3% of malignant adrenal tissue (P = .01). Molecular phenotypic expression was more heterogeneous in malignant than in normal (10 v five phenotypes) adrenal tissue. CONCLUSION: Meticulous morphologic evaluation, mitotic count, and tumor stage are essential in determining prognosis for patients with ACC. Multimolecular phenotyping demonstrates that the molecular complexity and heterogeneity of these neoplasms are such that targeted therapy needs to be patient specific.

scholarly journals The Landscape of MicroRNA, Piwi-Interacting RNA, and Circular RNA in Human Saliva

2015 ◽  
Vol 61 (1) ◽  
pp. 221-230 ◽  
Author(s):  
Jae Hoon Bahn ◽  
Qing Zhang ◽  
Feng Li ◽  
Tak-Ming Chan ◽  
Xianzhi Lin ◽  
...  
Keyword(s):  
Body Fluid ◽  
Expression Profiles ◽  
Embryonic Stem ◽  
Bioinformatic Analysis ◽  
Circular Rna ◽  
Human Saliva ◽  
Body Fluids ◽  
Individual Variability ◽  
Circular Rnas ◽  
Rna Seq

Abstract BACKGROUND Extracellular RNAs (exRNAs) in human body fluids are emerging as effective biomarkers for detection of diseases. Saliva, as the most accessible and noninvasive body fluid, has been shown to harbor exRNA biomarkers for several human diseases. However, the entire spectrum of exRNA from saliva has not been fully characterized. METHODS Using high-throughput RNA sequencing (RNA-Seq), we conducted an in-depth bioinformatic analysis of noncoding RNAs (ncRNAs) in human cell-free saliva (CFS) from healthy individuals, with a focus on microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), and circular RNAs (circRNAs). RESULTS Our data demonstrated robust reproducibility of miRNA and piRNA profiles across individuals. Furthermore, individual variability of these salivary RNA species was highly similar to those in other body fluids or cellular samples, despite the direct exposure of saliva to environmental impacts. By comparative analysis of &gt;90 RNA-Seq data sets of different origins, we observed that piRNAs were surprisingly abundant in CFS compared with other body fluid or intracellular samples, with expression levels in CFS comparable to those found in embryonic stem cells and skin cells. Conversely, miRNA expression profiles in CFS were highly similar to those in serum and cerebrospinal fluid. Using a customized bioinformatics method, we identified &gt;400 circRNAs in CFS. These data represent the first global characterization and experimental validation of circRNAs in any type of extracellular body fluid. CONCLUSIONS Our study provides a comprehensive landscape of ncRNA species in human saliva that will facilitate further biomarker discoveries and lay a foundation for future studies related to ncRNAs in human saliva.

IN VITRO RESPONSES OF FOCAL HYPERPLASTIC TISSUE OF THE HUMAN ADRENAL ZONA FASCICULATA TO ACTH

1977 ◽  
Vol 86 (2) ◽  
pp. 363-368 ◽  
Author(s):  
Kenneth V. Honn ◽  
Walter Chavin ◽  
Amnuay Singhakowinta
Keyword(s):  
Adrenocortical Function ◽  
Zona Fasciculata ◽  
Adrenal Tissue ◽  
Basal Cortisol ◽  
Aldosterone Production ◽  
Hyperplastic Tissue ◽  
Normal Human ◽  
Adrenal Zona Fasciculata ◽  
Normal Adrenal Tissue

ABSTRACT The temporal cAMP, cortisol and aldosterone responses to ACTH of focal hyperplasia of the zona fasciculata and of normal human adrenocortical tissue were investigated. ACTH significantly increased cAMP levels (1 min) and cortisol output (2 min) in normal adrenal tissue but not in hyperplastic tissue. However, following ACTH treatment cortisol and aldosterone production were depressed in the abnormal adrenal tissue below the untreated or the ACTH stimulated normal adrenal tissue. In addition, basal cortisol and aldosterone production of the hyperplastic adrenal tissue was elevated above that of the normal adrenal tissue. These findings suggest that the cAMP second messenger concept may be only one of several mechanisms in the modulation of human adrenocortical function.

scholarly journals Major hyperestrogenism in a feminizing adrenocortical adenoma despite a moderate overexpression of the aromatase enzyme

2003 ◽  
pp. 457-461 ◽  
Author(s):  
H Bouraima ◽  
B Lireux ◽  
H Mittre ◽  
A Benhaim ◽  
M Herrou ◽  
...  
Keyword(s):  
Rapid Development ◽  
High Dose ◽  
Aromatase Activity ◽  
Moderate Increase ◽  
Adrenocortical Adenoma ◽  
Rt Pcr ◽  
Adrenal Tissue ◽  
High Dose Dexamethasone ◽  
Normal Adrenal Tissue ◽  
Tomography Scan

A 30-year-old male was referred for the rapid development of gynecomastia, and dramatic hyperestrogenemia was assessed: plasma estrone, estradiol but also cortisol were not suppressed by high-dose dexamethasone, while gonadotropin pulsatility was completely abolished. A 60-mm right adrenal tumor was evidenced on computed tomography-scan, and the patient underwent adrenalectomy. The tumor was found to express a moderate increase in aromatase activity compared with adjacent non-neoplastic adrenal tissue. Quantitative RT-PCR also showed a weak and non-significant increase in total aromatase mRNA in the tumor compared with normal adrenal tissue. Aromatase transcripts were mainly promoter PII-derived, but different patterns of aromatase minor transcripts were found: promoter I.3- and I.6-derived transcripts were identified in the tumor, while only promoter I.4-derived transcripts were found in normal adrenal. This case report demonstrates that a sharp aromatase overexpression is not a prerequisite for clinical and biochemical hyperestrogenism, and further characterizes the aromatase promoter utilization in this feminizing adrenocortical tumor and in the normal adrenal cortex.

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