scholarly journals Peculiarities of placental microRNA expression in pregnancies complicated by gestational diabetes mellitus and preeclampsia

2017 ◽  
Vol 66 (3) ◽  
pp. 110-115
Author(s):  
Vladimir S. Pakin ◽  
Elena S. Vashukova ◽  
Roman V. Kapustin ◽  
Olga N. Arzhanova ◽  
Andrey S. Glotov ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Comparative Analysis ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Mirna Expression Profiles ◽  
Mirnas Expression ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
In Pregnancy

The aim of study was to determine feasible changes of placental miRNAs expression profiles revealed by next generation sequencing (NGS) in pregnancies with GDM complicated or not with PE. Out of 27 miRNAs, studied expression was significantly different (FDR < 0.05) only for his-miR-45a. Comparative analysis of revealed reliable differences in expression of hsa-miR-4532 (p < 0.0001, FDR = 0.0008), hsa-miR-34c-5p (p < 0.0001, FDR = 0.0083), and hsa-miR-193b-5p (p < 0.0001, FDR = 0.0139) in pregnancy complicated by PE, without of GDM. The present results suggest that GDM and PE are associated with specific alterations in the placental miRNA expression profiles. Further studies are needed to verify the role of these microRNA in molecular mechanisms underlying GDM and PE pathogenesis.

scholarly journals Omics-Based Identification of Shared and Gender Disparity Routes in Hras12V-Induced Hepatocarcinogenesis: An Important Role for Dlk1-Dio3 Genomic Imprinting Region

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Zhang ◽  
Huiling Li ◽  
Jianyi Dong ◽  
Nan Zhang ◽  
Yang Liu ◽  
...  
Keyword(s):  
Genomic Imprinting ◽  
Expression Profiles ◽  
Normal Liver ◽  
Gender Disparity ◽  
Hepatic Carcinogenesis ◽  
Mirna Expression Profiles ◽  
Differentially Expressed Mirnas ◽  
And Gender ◽  
Next Generation Sequencing Ngs

The phenomenon of gender disparity is very profound in hepatocellular carcinoma (HCC). Although previous research has revealed important roles of microRNA (miRNA) in HCC, there are no studies investigating the role of miRNAs in gender disparity observed hepatocarcinogenesis. In the present study, we investigated the global miRNAomics changes related to Ras-induced male-prevalent hepatocarcinogenesis in a Hras12V-transgenic mouse model (Ras-Tg) by next-generation sequencing (NGS). We identified shared by also unique changes in miRNA expression profiles in gender-dependent hepatocarcinogenesis. Two hundred sixty-four differentially expressed miRNAs (DEMIRs) with q value ≤0.05 and fold change ≥2 were identified. A vertical comparison revealed that the lower numbers of DEMIRs in the hepatic tumor (T) compared with the peri-tumor precancerous tissue (P) of Ras-Tg and normal liver tissue of wild-type C57BL/6J mice (W) in males indicated that males are more susceptible to develop HCC. The expression pattern analysis revealed 43 common HCC-related miRNAs and 4 Ras-positive-related miRNAs between males and females. By integrating the mRNA transcriptomic data and using 3-node FFL analysis, a group of significant components commonly contributing to HCC between sexes were filtered out. A horizontal comparison showed that the majority of DEMIRs are located in the Dlk1-Dio3 genomic imprinting region (GIR) and that they are closely related to not only hepatic tumorigenesis but also to gender disparity in hepatocarcinogenesis. This is achieved by regulating multiple metabolic pathways, including retinol, bile acid, and steroid hormones. In conclusion, the identification of shared and gender-dependent DEMIRs in hepatocarcinogenesis provides valuable insights into the mechanisms that contribute to male-biased Ras-induced hepatic carcinogenesis.

scholarly journals Putative Role of MicroRNA-Regulated Pathways in Comorbid Neurological and Cardiovascular Disorders

2009 ◽  
Vol 2009 ◽  
pp. 1-5 ◽  
Author(s):  
Sébastien S. Hébert
Keyword(s):  
Mirna Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Heart Cell ◽  
Cardiovascular Disorders ◽  
Increased Risk ◽  
Mirna Expression Profiles ◽  
And Function ◽  
The Brain

Background. The conserved noncoding microRNAs (miRNAs) that function to regulate gene expression are essential for the development and function of the brain and heart. Changes in miRNA expression profiles are associated with an increased risk for developing neurodegenerative disorders as well as heart failure. Here, the hypothesis of how miRNA-regulated pathways could contribute to comorbid neurological and cardiovascular disorders will be discussed. Presentation. Changes in miRNA expression occurring in the brain and heart could have an impact on coexisting neurological and cardiovascular characteristics by (1) modulating organ function, (2) accentuating cellular stress, and (3) impinging on neuronal and/or heart cell survival. Testing. Evaluation of miRNA expression profiles in the brain and heart tissues from individuals with comorbid neurodegenerative and cardiovascular disorders will be of great importance and relevance. Implications. Careful experimental design will shed light to the deeper understanding of the molecular mechanisms tying up those different but yet somehow connected diseases.

scholarly journals Omics-based identification of shared and gender disparity routes in Hras12V-induced hepatocarcinogenesis: an important role for Dlk1-Dio3 genomic imprinting region

2020 ◽  
Author(s):  
Huiling Li ◽  
Jing Zhang ◽  
Jianyi Dong ◽  
Xu Zheng ◽  
Chuanyi Lei ◽  
...  
Keyword(s):  
Genomic Imprinting ◽  
Expression Profiles ◽  
Normal Liver ◽  
Gender Disparity ◽  
Hepatic Carcinogenesis ◽  
Mirna Expression Profiles ◽  
Differentially Expressed Mirnas ◽  
And Gender ◽  
Next Generation Sequencing Ngs

Abstract Background: The phenomenon of gender disparity is very profound in hepatocellular carcinoma (HCC). Although previous research has revealed important roles of microRNA (miRNA) in HCC, there are no studies investigating the role of miRNAs in gender disparity observed hepatocarcinogenesis. Results: In the present study, we investigated the global miRNAomics changes related to Ras -induced male-prevalent hepatocarcinogenesis in a Hras12V -transgenic mouse model ( Ras -Tg) by next-generation sequencing (NGS). We identified shared by also unique changes in miRNA expression profiles in gender-dependent hepatocarcinogenesis. 264 differentially expressed miRNAs ( DEMIRs) with q value ≤ 0.05 and fold change ≥ 2 were identified. A vertical comparison revealed that the lower numbers of DEMIRs in the hepatic tumor (T) compared with the peri-tumor precancerous tissue (P) of Ras -Tg and normal liver tissue of wild-type C57BL/6J mice (W) in males indicated that males are more susceptible to develop HCC. The expression pattern analysis revealed 43 common HCC-related miRNAs and 4 Ras -positive-related miRNAs between males and females. By integrating the mRNA transcriptomic data and using 3-node FFL analysis, a group of significant components commonly contributing to HCC between sexes were filtered out. A horizontal comparison showed that the majority of DEMIRs are located in the Dlk1-Dio3 genomic imprinting region (GIR) and that they are closely related to not only hepatic tumorigenesis but also to gender disparity in hepatocarcinogenesis. This is achieved by regulating multiple metabolic pathways, including retinol, bile acid, and steroid hormones. Conclusions: In conclusion, the identification of shared and gender-dependent DEMIRs in hepatocarcinogenesis provides valuable insights into the mechanisms that contribute to male-biased Ras -induced hepatic carcinogenesis.

scholarly journals CSF3R T618I, SETBP1 G870S, SRSF2 P95H, and ASXL1 Q780* tetramutation co-contribute to myeloblast transformation in a chronic neutrophilic leukemia

2021 ◽  
Author(s):  
Yi Qian ◽  
Yan Chen ◽  
Xiaoming Li
Keyword(s):  
Alpha Interferon ◽  
Past Medical History ◽  
Variant Allele Frequency ◽  
Significant Past Medical History ◽  
Chronic Neutrophilic Leukemia ◽  
Hypercellular Marrow ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Stat Pathway

AbstractChronic neutrophilic leukemia (CNL) is a rare but serious myeloid malignancy. In a review of reported cases for WHO-defined CNL, CSF3R mutation is found in about 90% cases and confirmed as the molecular basis of CNL. Concurrent mutations are observed in CSF3R-mutated CNL patients, including ASXL1, SETBP1, SRSF2, JAK2, CALR, TET2, NRAS, U2AF1, and CBL. Both ASXL1 and SETBP1 mutations in CNL have been associated with a poor prognosis, whereas, SRSF2 mutation was undetermined. Our patient was a 77-year-old man and had no significant past medical history and symptoms with leukocytosis. Bone marrow (BM) aspirate and biopsy revealed a markedly hypercellular marrow with prominent left-shifted granulopoiesis. Next-generation sequencing (NGS) of DNA from the BM aspirate of a panel of 28 genes, known to be pathogenic in MDS/MPN, detected mutations in CSF3R, SETBP1, and SRSF2, and a diagnosis of CNL was made. The patient did not use a JAK-STAT pathway inhibitor (ruxolitinib) but started on hydroxyurea and alpha-interferon and developed pruritus after 4 months of diagnosis and nasal hemorrhage 1 month later. Then, the patient was diagnosed with CNL with AML transformation and developed intracranial hemorrhage and died. We repeated NGS and found that three additional mutations were detected: ASXL1, PRKDC, MYOM2; variant allele frequency (VAF) of the prior mutations in CSF3R, SETBP1, and SRSF2 increased. The concurrence of CSF3RT618I, ASXL1, SETBP1, and SRSF2 mutation may be a mutationally detrimental combination and contribute to disease progression and AML transformation, as well as the nonspecific treatment of hydroxyurea and alpha-interferon, but the significance and role of PRKDC and MYOM2 mutations were not undetermined.

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 The p53/miR-34a/SIRT1 Positive Feedback Loop in Quercetin-Induced Apoptosis

2015 ◽  
Vol 35 (6) ◽  
pp. 2192-2202 ◽  
Author(s):  
Guohua Lou ◽  
Yanning Liu ◽  
Shanshan Wu ◽  
Jihua Xue ◽  
Fan Yang ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Feedback Loop ◽  
Molecular Mechanisms ◽  
Rt Pcr ◽  
Cycle Arrest ◽  
Anticancer Effects ◽  
Huh7 Cells ◽  
Mirnas Expression ◽  
Induced Apoptosis

Background: The anti-tumor effects of quercetin have been reported, but the underlying molecular mechanisms remain to be elucidated. The aim of present study was to explore the role of miRNA in the anticancer effects of quercetin. Methods: The differential miRNAs expression between the HepG2 and Huh7 cells treated by quercetin were detected by microarray. The xCELLigence, Flow cytometry, RT-PCR and Western blot were used to analyze the cell proliferation, cell apoptosis, cell cycle arrest, anti-tumor genes, and protein expression. Results: miR-34a was up-regulated in HepG2 cells treated by quercetin exhibiting wild-type p53. When inhibiting the miR-34a, the sensitivity of the cells to quercetin decreased and the expression of the SIRT1 was up-regulated, but the acetylation of p53 and the expression of some genes related to p53 down-regulated. Conclusion: miR-34a plays an important role in the anti-tumor effects of querctin in HCC, miR-34a may be a tiemolecule between the p53 and SIRT1 and is composed of a p53/miR-34a/SIRT1 signal feedback loop, which could enhance apoptosis signal and significantly promote cell apoptosis.

Machine Learning Perspective in Cancer Research

2021 ◽  
pp. 142-163
Author(s):  
Aman Sharma ◽  
Rinkle Rani
Keyword(s):  
Machine Learning ◽  
Cancer Research ◽  
Expression Profiles ◽  
Genetic Diseases ◽  
Cost Effective ◽  
Healthcare Sector ◽  
Diagnosis And Prognosis ◽  
Cost Effective Approach ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Advancement in genome sequencing technology has empowered researchers to think beyond their imagination. Researchers are trying their hard to fight against various genetic diseases like cancer. Artificial intelligence has empowered research in the healthcare sector. Moreover, the availability of opensource healthcare datasets has motivated the researchers to develop applications which can help in early diagnosis and prognosis of diseases. Further, next-generation sequencing (NGS) has helped to look into detailed intricacies of biological systems. It has provided an efficient and cost-effective approach with higher accuracy. The advent of microRNAs also known as small noncoding genes has begun the paradigm shift in oncological research. We are now able to profile expression profiles of RNAs using RNA-seq data. microRNA profiling has helped in uncovering their relationship in various genetic and biological processes. Here in this chapter, the authors present a review of the machine learning perspective in cancer research.

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