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

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.

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

10.21203/rs.2.23077/v1 ◽

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.

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

Journal of obstetrics and women s diseases ◽

10.17816/jowd663110-115 ◽

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.

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Identification of differentially expressed microRNAs in outgrowth embryos compared with blastocysts and non-outgrowth embryos in mice

Reproduction Fertility and Development ◽

10.1071/rd18161 ◽

2019 ◽

Vol 31 (4) ◽

pp. 645 ◽

Cited By ~ 6

Author(s):

Jihyun Kim ◽

Jaewang Lee ◽

Jin Hyun Jun

Keyword(s):

Bioinformatics Analysis ◽

Preimplantation Embryo ◽

Expression Profiles ◽

In Silico Analysis ◽

Differentially Expressed ◽

Recurrent Implantation Failure ◽

Preimplantation Embryo Development ◽

Mirna Expression Profiles ◽

Differentially Expressed Mirnas ◽

Silico Analysis

Recurrent implantation failure (RIF) is one of the main causes for the repeated failure of IVF, and the major reason for RIF is thought to be a miscommunication between the embryo and uterus. However, the exact mechanism underlying embryo–uterus cross-talk is not fully understood. The aim of the present study was to identify differentially expressed microRNAs (miRNAs) among blastocysts, non-outgrowth and outgrowth embryos in mice using microarray analysis. A bioinformatics analysis was performed to predict the potential mechanisms of implantation. The miRNA expression profiles differed significantly between non-outgrowth and outgrowth embryos. In all, 3163 miRNAs were detected in blastocysts and outgrowth embryos. Of these, 10 miRNA candidates (let-7b, miR-23a, miR-27a, miR-92a, miR-183, miR-200c, miR-291a, miR-425, miR-429 and miR-652) were identified as significant differentially expressed miRNAs of outgrowth embryos by in silico analysis. The expression of the miRNA candidates was markedly changed during preimplantation embryo development. In particular, let-7b-5p, miR-200c-3p and miR-23a-3p were significantly upregulated in outgrowth embryos compared with non-outgrowth blastocysts. Overall, differentially expressed miRNAs in outgrowth embryos compared with blastocysts and non-outgrowth embryos could be involved in embryo attachment, and interaction between the embryo proper and maternal endometrium during the implantation process.

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Socio-cultural Causes of Gender Disparity in Nepalese Society

Journal of Advanced Academic Research ◽

10.3126/jaar.v2i1.16601 ◽

2017 ◽

Vol 2 (1) ◽

pp. 100-111

Author(s):

Anita Shrestha ◽

Ritu Prasad Gartoulla

Keyword(s):

Ethnic Groups ◽

Gender Disparity ◽

Cultural Perspective ◽

Religious Activities ◽

Political Awareness ◽

The Government ◽

Gender Based ◽

And Gender ◽

Cultural Causes

Gender is socially constructed idea and disparity is the problem created by the society. The study was conducted from the socio-cultural perspective so the main objective of this study was to identify the socio-cultural causes of gender disparity in five different ethnic groups: Newar, Magar, Tamang, Rai/Limbu and Brahmin/Chhetri of Kathmandu Valley. Total 390 respondents were selected randomly from the all ethnic groups. Except the role of religion, the role of culture, patriarchy system, social perception, sources of income, level of education, political awareness & involvement and gender based division of labor had significant effect to increase the gender disparity in society. Political announcement that Nepal as a secular country had effected in the perception and practices related to the religious activities of people also. The government should address the socio-cultural problem and further researcher should explore the strategies to address the problem of gender disparity.

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MicroRNA expression patterns associated with hyperfunctioning and non-hyperfunctioning phenotypes in adrenocortical adenomas

Acta Endocrinologica ◽

10.1530/eje-13-0817 ◽

2014 ◽

Vol 170 (4) ◽

pp. 583-591 ◽

Cited By ~ 12

Author(s):

David Velázquez-Fernández ◽

Stefano Caramuta ◽

Deniz M Özata ◽

Ming Lu ◽

Anders Höög ◽

...

Keyword(s):

Mirna Expression ◽

Expression Profiles ◽

Expression Patterns ◽

Gene Mutations ◽

Mirna Expression Profile ◽

Differentially Expressed ◽

Adrenocortical Adenoma ◽

Tumor Subtypes ◽

Mirna Expression Profiles ◽

Differentially Expressed Mirnas

BackgroundThe adrenocortical adenoma (ACA) entity includes aldosterone-producing adenoma (APA), cortisol-producing adenoma (CPA), and non-hyperfunctioning adenoma (NHFA) phenotypes. While gene mutations and mRNA expression profiles have been partly characterized, less is known about the alterations involving microRNA (miRNA) expression.AimTo characterize miRNA expression profile in relation to the subtypes of ACAs.Subjects and methodsmiRNA expression profiles were determined in 26 ACAs (nine APAs, ten CPAs, and seven NHFAs) and four adrenal references using microarray-based screening. Significance analysis of microarrays (SAM) was carried out to identify differentially expressed miRNAs between ACA and adrenal cortices or between tumor subtypes. Selected differentially expressed miRNAs were validated in an extended series of 43 ACAs and ten adrenal references by quantitative RT-PCR.ResultsAn hierarchical clustering revealed separate clusters for APAs and CPAs, while the NHFAs were found spread out within the APA/CPA clusters. When NHFA was excluded, the clustering analysis showed a better separation between APA and CPA. SAM analysis identified 40 over-expressed and three under-expressed miRNAs in the adenomas as compared with adrenal references. Fourteen miRNAs were common among the three ACA subtypes. Furthermore, we found specific miRNAs associated with different tumor phenotypes.ConclusionThe results suggest that miRNA expression profiles can distinguish different subtypes of ACA, which may contribute to a deeper understanding of ACA development and potential therapeutics.

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Renal Tissue miRNA Expression Profiles in ANCA-Associated Vasculitis—A Comparative Analysis

International Journal of Molecular Sciences ◽

10.3390/ijms23010105 ◽

2021 ◽

Vol 23 (1) ◽

pp. 105

Author(s):

Matic Bošnjak ◽

Željka Večerić-Haler ◽

Emanuela Boštjančič ◽

Nika Kojc

Keyword(s):

Mirna Expression ◽

Expression Profiles ◽

Target Organ Damage ◽

Organ Damage ◽

Renal Tissue ◽

Differentially Expressed ◽

Tissue Samples ◽

Anca Associated Vasculitis ◽

Mirna Expression Profiles ◽

Differentially Expressed Mirnas

Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) comprises autoimmune disease entities that cause target organ damage due to relapsing-remitting small vessel necrotizing vasculitis, and which affects various vascular beds. The pathogenesis of AAV is incompletely understood, which translates to considerable disease- and treatment-related morbidity and mortality. Recent advances have implicated microRNAs (miRNAs) in AAV; however, their accurate characterization in renal tissue is lacking. The goal of this study was to identify the intrarenal miRNA expression profile in AAV relative to healthy, non-inflammatory and inflammatory controls to identify candidate-specific miRNAs. Formalin-fixed, paraffin-embedded renal biopsy tissue samples from 85 patients were obtained. Comprehensive miRNA expression profiles were performed using panels with 752 miRNAs and revealed 17 miRNA that differentiated AAV from both controls. Identified miRNAs were annotated to characterize their involvement in pathways and to define their targets. A considerable subset of differentially expressed miRNAs was related to macrophage and lymphocyte polarization and cytokines previously deemed important in AAV pathogenesis, lending credence to the obtained results. Interestingly, several members of the miR-30 family were detected. However, a validation study of these differentially expressed miRNAs in an independent, larger sample cohort is needed to establish their potential diagnostic utility.

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Chromosome mapping of five differently expressed miRNAs in porcine skeletal muscle development (Brief Report)

Archives Animal Breeding ◽

10.5194/aab-53-734-2010 ◽

2010 ◽

Vol 53 (6) ◽

pp. 734-736

Author(s):

H. B. He ◽

S. H. Zhao ◽

X. Y. Li

Keyword(s):

Skeletal Muscle ◽

Muscle Development ◽

Expression Profiles ◽

Chromosome Mapping ◽

Differentially Expressed ◽

Skeletal Muscle Development ◽

Regulate Gene Expression ◽

Mirna Expression Profiles ◽

Differentially Expressed Mirnas ◽

Regulatory Rnas

Abstract. MicroRNAs (miRNAs) are a class of short, non-coding regulatory RNAs, which are approximately 22 nucleotides in length. Typically, miRNAs negatively regulate gene expression by binding with the 3' untranslated region (UTR) of its regulatory target mRNAs. MicroRNAs are known to play diverse roles in fundamental biological processes, such as proliferation, differentiation and apoptosis (Bartel 2004, 2009). It has been reported that miR-1, miR-133, miR-181 and miR-206 play important roles in skeletal muscle proliferation and hypertrophy (Callis et al. 2007, McCarthy -Esser 2007). We have detected porcine miRNA expression profiles during different stage of skeletal muscle development and a total of 140 miRNAs were differentially expressed (HUANG et al. 2008). In this study, we mapped five differentially expressed miRNAs (mir-29c, mir-103-1, mir-127, mir-193b and mir-218-1) using the radiation hybrid (IMpRH) panel (YERLE et al. 1998).

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The Oncogenic Role of miR-BART19-3p in Epstein-Barr Virus-Associated Diseases

BioMed Research International ◽

10.1155/2020/5217039 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Qingxun Zhang ◽

Donghua Luo ◽

Zhengde Xie ◽

Hongxuan He ◽

Ziyuan Duan

Keyword(s):

Cancer Progression ◽

Expression Profiles ◽

Ectopic Expression ◽

Biological Significance ◽

Barr Virus ◽

Associated Diseases ◽

Mirna Expression Profiles ◽

Direct Target ◽

Epstein Barr

Accumulating evidence so far has shown that EBV’s miRNAs have been found to be involved in cancer progression. However, the comprehensive EBV miRNA expression profiles and their biological significance in EBV-associated diseases are not well documented. A comprehensive profiling of EBV-encoded miRNAs expressed in CAEBV, EBV-HLH, and nasopharyngeal carcinoma (NPC) patients was constructed, and the results showed that miR-BART19-3p was upregulated in all these diseases. Ectopic expression of miR-BART19-3p induced EBV-negative cell proliferation and suppressed cell apoptosis. Molecularly, adenomatous polyposis coli (APC) was identified to be a direct target of miR-BART19-3p, and APC mRNA expression was inversely correlated with miR-BART19-3p in CAEBV samples. Our results demonstrated that miR-BART19-3p contributes to the tumorigenesis of EBV-associated diseases and may be a potential therapeutic target.

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Downregulated Platelet miR-1233-5p in Patients with Alzheimer’s Pathologic Change with Mild Cognitive Impairment is Associated with Aβ-Induced Platelet Activation via P-Selectin

Journal of Clinical Medicine ◽

10.3390/jcm9061642 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1642

Author(s):

Bo Kyung Lee ◽

Min Hee Kim ◽

Sang Yoon Lee ◽

Sang Joon Son ◽

Chang Hyung Hong ◽

...

Keyword(s):

Cognitive Impairment ◽

Cell Adhesion ◽

Mild Cognitive Impairment ◽

Expression Profiles ◽

Human Platelets ◽

Pathologic Change ◽

Cognitively Normal ◽

Normal Individuals ◽

Mirna Expression Profiles

MicroRNAs (miRNAs) have been proposed as a promising biomarker for various diseases including Alzheimer’s disease (AD). More attention has recently been focused on the diagnosis and treatment at earlier stage of mild cognitive impairment (MCI) for preventing its progression to AD. To identify potential pathologic markers for Aβ(+)MCI (Alzheimer’s pathologic change with MCI), we investigated miRNA expression profiles in the platelets from patients with Aβ(+)MCI, in comparison with those from Aβ(−)MCI (Non-Alzheimer’s pathologic change with MCI) and CNI (cognitively normal individuals). We found that let-7i-5p, miR-125a, miR-1233-5p, and miR-6787-5p were significantly downregulated, while miR-6880-5p expression was upregulated. Of these, only miR-1233-5p was significantly downregulated by Aβ treatment in both human platelets and their precursor megakaryocytes (MEG-01 cells). We explored the role of miRNAs by using miRNA mimics or inhibitors, and found that the diminished level of miR-1233-5p was associated with Aβ-induced increase in the expression of P-selectin and cell adhesion to fibronectin. Our results further indicated that Aβ-induced increase in platelet/MEG adhesion to fibronectin is likely mediated via P-selectin. In conclusion, this study suggests the downregulation of platelet-derived miR-1233-5p as a pathologic marker for Aβ(+)MCI.

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Detection of Differentially Expressed MicroRNAs in Rheumatic Heart Disease: miR-1183 and miR-1299 as Potential Diagnostic Biomarkers

BioMed Research International ◽

10.1155/2015/524519 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Ni Li ◽

Jiangfang Lian ◽

Sheng Zhao ◽

Dawei Zheng ◽

Xi Yang ◽

...

Keyword(s):

Heart Disease ◽

Pulmonary Artery ◽

Rheumatic Heart Disease ◽

Mirna Expression ◽

Expression Profiles ◽

Differentially Expressed ◽

Mirna Expression Profiles ◽

Differentially Expressed Mirnas ◽

Secondary Pulmonary Hypertension ◽

Rheumatic Heart

This study compared microRNA (miRNA) expression profiles between rheumatic heart disease (RHD) patients and healthy controls to investigate their differential expression and help elucidate their mechanisms of action. Microarray analysis was used to measure miRNA expression, and a total of 133 miRNAs were shown to be significantly upregulated in RHD patients compared with controls, including miR-1183 and miR-1299. A total of 137 miRNAs, including miR-4423-3p and miR-218-1-3p, were significantly downregulated in RHD patients. Quantitative real-time-PCR confirmed microarray findings for miR-1183 and miR-1299 in both tissue and plasma. Bioinformatic predictions were also made of differentially expressed miRNAs as biomarkers in RHD by databases and GO/pathway analysis. Furthermore, we investigated miR-1183 and miR-1299 expression in RHD patients with secondary pulmonary hypertension (PAH). Our findings identified an important role for miR-1299 as a direct regulator of RHD, while the observed difference in expression of miR-1183 between RHD-PAH patients with high or low pulmonary artery pressure suggests that miR-1183 overexpression may reflect pulmonary artery remodeling. miR-1183 and miR-1299 appear to play distinct roles in RHD pathogenesis accompanied by secondary PAH and could be used as potential biological markers for disease development.

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