Analysis of whole genome-wide microRNA transcriptome profiling in invasive pituitary adenomas and non-invasive pituitary adenomas

Abstract Background Dysregulation of microRNAs (miRNAs) plays a critical role during the occurrence and progress of pituitary adenomas (PAs). However, the roles of miRNAs in the invasiveness of PA are poorly understood. This study aims to more comprehensively and specific define the relationship between altered miRNA and PA invasion. Methods The differential expression of miRNAs (DEMs) between invasive PAs (IPAs) and non-invasive PAs (NPAs) was explored by RNA sequencing and which functions were analyzed by gene ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG). The miRNA-mRNA network was predicted with bioinformatics. Results We identified 31 upregulated miRNAs and 24 downregulated miRNAs in IPAs compared with NPAs. GO analysis and KEGG pathway analysis showed the DEMs were mainly associated with cell proliferation and cell cycle pathway. In addition, on the count of predicted miRNA-mRNA network, two hub miRNAs were identified. Conclusions Our results demonstrate the miRNA-mRNA network in detail, which suggest that miRNA may be a promising target in diagnosis and therapy for IPAs.

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The Potential circRNAs in Imatinib Resistance of GIST

10.21203/rs.3.rs-966710/v1 ◽

2021 ◽

Author(s):

Jingyi Yan ◽

Xiaolei Chen ◽

Qiantong Dong ◽

Ji Lin ◽

Xuecheng Sun

Keyword(s):

Critical Role ◽

Resistance Mechanism ◽

Circular Rnas ◽

Imatinib Resistance ◽

Secondary Resistance ◽

Primary Gist ◽

Kegg Pathway Analysis ◽

Tumor Tissues ◽

Competing Endogenous Rna Network ◽

The Relationship

Abstract Background: Circular RNAs are a recently (re-)discovered abundant RNA species, belongs to part of the competing endogenous RNA network(ceRNA), Which was proved to play a critical role in the development, diagnosis and progress of diseases. Methods: We analyzed the expression of circular RNAs in paired normal gastric tissues(N), primary GIST (gastrointestinal stromal tumor) tissues (Y or YC) and imatinib mesylate secondary resistance GIST tissues(C) with microarray and predicted 8677 dysregulated circular RNAs. Results: We identified 15 circRNAs was up-regulated and 8 circRNAs were down-regulated in C group. Gene ontology (GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified that the host linear transcripts of these differentially expressed circRNAs were involved in many critical biological pathways and molecular functions, predicting the potential tumor-genesis and drug resistance mechanism was related with HIF-1 pathway, later we draw the cirRNA-miRNA-mRNA network involved in the HIF-1 pathway, found that several dysregulated circRNAs and the relationship between circRNA-miRNAs-mRNA, such as circRNA_06551, circRNA_14668, circRNA_04497, circRNA_08683, circRNA_09923(Green, down-regulation) and circRNA_23636, circRNA_15734(Red, up-regulation). Conclusions: Taken together, we identified a panel of dysregulated circRNAs that may be potential biomarkers even therapy relevant to the GIST, especially imatinib secondary resistance GIST.

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MicroRNAs as Potential Biomarkers in Pituitary Adenomas

Non-Coding RNA ◽

10.3390/ncrna7030055 ◽

2021 ◽

Vol 7 (3) ◽

pp. 55

Author(s):

Simone Donati ◽

Cinzia Aurilia ◽

Gaia Palmini ◽

Francesca Miglietta ◽

Irene Falsetti ◽

...

Keyword(s):

Pituitary Adenomas ◽

Expression Patterns ◽

Critical Role ◽

Improve Patient Care ◽

Therapeutic Strategies ◽

Transcriptional Level ◽

Regulate Gene Expression ◽

Non Invasive ◽

Pituitary Tumorigenesis ◽

Improve Patient

Pituitary adenomas (PAs) are one of the most common lesions of intracranial neoplasms, occurring in approximately 15% of the general population. They are typically benign, although some adenomas show aggressive behavior, exhibiting rapid growth, drug resistance, and invasion of surrounding tissues. Despite ongoing improvements in diagnostic and therapeutic strategies, late first diagnosis is common, and patients with PAs are prone to relapse. Therefore, earlier diagnosis and prevention of recurrence are of importance to improve patient care. MicroRNAs (miRNAs) are short non-coding single stranded RNAs that regulate gene expression at the post-transcriptional level. An increasing number of studies indicate that a deregulation of their expression patterns is related with pituitary tumorigenesis, suggesting that these small molecules could play a critical role in contributing to tumorigenesis and the onset of these tumors by acting either as oncosuppressors or as oncogenes, depending on the biological context. This paper provides an overview of miRNAs involved in PA tumorigenesis, which might serve as novel potential diagnostic and prognostic non-invasive biomarkers, and for the future development of miRNA-based therapeutic strategies for PAs.

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Migraine: Genetic Variants and Clinical Phenotypes

Current Medicinal Chemistry ◽

10.2174/0929867325666180719120215 ◽

2019 ◽

Vol 26 (34) ◽

pp. 6207-6221 ◽

Cited By ~ 1

Author(s):

Innocenzo Rainero ◽

Alessandro Vacca ◽

Flora Govone ◽

Annalisa Gai ◽

Lorenzo Pinessi ◽

...

Keyword(s):

Genetic Variants ◽

Association Studies ◽

Mthfr Gene ◽

Genome Wide Association Studies ◽

Clinical Phenotypes ◽

Network Analyses ◽

Genome Wide ◽

Genomic Studies ◽

The Common ◽

The Relationship

Migraine is a common, chronic neurovascular disorder caused by a complex interaction between genetic and environmental risk factors. In the last two decades, molecular genetics of migraine have been intensively investigated. In a few cases, migraine is transmitted as a monogenic disorder, and the disease phenotype cosegregates with mutations in different genes like CACNA1A, ATP1A2, SCN1A, KCNK18, and NOTCH3. In the common forms of migraine, candidate genes as well as genome-wide association studies have shown that a large number of genetic variants may increase the risk of developing migraine. At present, few studies investigated the genotype-phenotype correlation in patients with migraine. The purpose of this review was to discuss recent studies investigating the relationship between different genetic variants and the clinical characteristics of migraine. Analysis of genotype-phenotype correlations in migraineurs is complicated by several confounding factors and, to date, only polymorphisms of the MTHFR gene have been shown to have an effect on migraine phenotype. Additional genomic studies and network analyses are needed to clarify the complex pathways underlying migraine and its clinical phenotypes.

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XIST: A Meaningful Long Noncoding RNA in NSCLC Process

Current Pharmaceutical Design ◽

10.2174/1381612826999201202102413 ◽

2020 ◽

Vol 26 ◽

Author(s):

Yujie Shen ◽

Yexiang Lin ◽

Kai Liu ◽

Jinlan Chen ◽

Juanjuan Zhong ◽

...

Keyword(s):

Therapeutic Target ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Critical Role ◽

Biological Functions ◽

Potential Therapeutic Target ◽

Considerable Evidence ◽

Lncrna Xist ◽

Nsclc Patients ◽

The Relationship

Background: A number of studies have proposed that lncRNA XIST plays a role in the development and chemosensitivity of NSCLC. Besides, XIST may become a potential therapeutic target for NSCLC patients. The aim of this review is to reveal the biological functions and exact mechanisms of XIST in NSCLC. Methods: In this review, relevant researches involving in the relationship between XIST and NSCLC are collected through systematic retrieval of PubMed Results: XIST is an oncogene in NSCLC and is abnormally upregulated in NSCLC tissues. Considerable evidence has shown that XIST exerts a critical role in the proliferation, invasion, migration, apoptosis and chemosensitivity of NSCLC cells. XIST mainly functions as a ceRNA in NSCLC process, while XIST also functions at transcriptional levels. Conclusion: LncRNA XIST has potential to become a novel biomolecular marker of NSCLC and a therapeutic target for NSCLC.

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Endothelial Dysfunction and Inflammatory Markers of Vascular Disease

Current Vascular Pharmacology ◽

10.2174/1570161118666200421142542 ◽

2020 ◽

Vol 19 (3) ◽

pp. 243-249 ◽

Cited By ~ 1

Author(s):

Sevket Balta

Keyword(s):

Endothelial Dysfunction ◽

Vascular Disease ◽

Inflammatory Markers ◽

Vascular Diseases ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Non Invasive ◽

Von Willebrand ◽

The Relationship ◽

Willebrand Factor

: Vascular diseases are the main reason for morbidity and mortality worldwide. As we know, the earlier phase of vascular diseases is endothelial dysfunction in humans, the endothelial tissues play an important role in inflammation, coagulation, and angiogenesis, via organizing ligand-receptor associations and the various mediators’ secretion. We can use many inflammatory non-invasive tests (flowmediated dilatation, epicedial fat thickness, carotid-intima media thickness, arterial stiffness and anklebrachial index) for assessing the endothelial function. In addition, many biomarkers (ischemia modified albumin, pentraxin-3, E-selectin, angiopoietin, endothelial cell specific molecule 1, asymmetrical dimethylarginine, von Willebrand factor, endothelial microparticles and endothelial progenitor cells) can be used to evaluate endothelial dysfunction. We have focused on the relationship between endothelial dysfunction and inflammatory markers of vascular disease in this review.

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Genome-wide identification of cyclin-dependent kinase (CDK) genes affecting adipocyte differentiation in cattle

BMC Genomics ◽

10.1186/s12864-021-07653-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Cuili Pan ◽

Zhaoxiong Lei ◽

Shuzhe Wang ◽

Xingping Wang ◽

Dawei Wei ◽

...

Keyword(s):

Gene Family ◽

Expression Analysis ◽

Adipocyte Differentiation ◽

Bos Taurus ◽

Adipogenic Differentiation ◽

Critical Role ◽

Bos Indicus ◽

Specific Expression ◽

Genome Wide ◽

A Genome

Abstract Background Cyclin-dependent kinases (CDKs) are protein kinases regulating important cellular processes such as cell cycle and transcription. Many CDK genes also play a critical role during adipogenic differentiation, but the role of CDK gene family in regulating bovine adipocyte differentiation has not been studied. Therefore, the present study aims to characterize the CDK gene family in bovine and study their expression pattern during adipocyte differentiation. Results We performed a genome-wide analysis and identified a number of CDK genes in several bovine species. The CDK genes were classified into 8 subfamilies through phylogenetic analysis. We found that 25 bovine CDK genes were distributed in 16 different chromosomes. Collinearity analysis revealed that the CDK gene family in Bos taurus is homologous with Bos indicus, Hybrid-Bos taurus, Hybrid Bos indicus, Bos grunniens and Bubalus bubalis. Several CDK genes had higher expression levels in preadipocytes than in differentiated adipocytes, as shown by RNA-seq analysis and qPCR, suggesting a role in the growth of emerging lipid droplets. Conclusion In this research, 185 CDK genes were identified and grouped into eight distinct clades in Bovidae, showing extensively homology. Global expression analysis of different bovine tissues and specific expression analysis during adipocytes differentiation revealed CDK4, CDK7, CDK8, CDK9 and CDK14 may be involved in bovine adipocyte differentiation. The results provide a basis for further study to determine the roles of CDK gene family in regulating adipocyte differentiation, which is beneficial for beef quality improvement.

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Genome-wide CRISPR/Cas9 screening identifies CARHSP1 responsible for radiation resistance in glioblastoma

Cell Death and Disease ◽

10.1038/s41419-021-04000-3 ◽

2021 ◽

Vol 12 (8) ◽

Author(s):

Guo-dong Zhu ◽

Jing Yu ◽

Zheng-yu Sun ◽

Yan Chen ◽

Hong-mei Zheng ◽

...

Keyword(s):

Cold Shock ◽

Mrna Level ◽

Critical Role ◽

Inflammatory Signaling ◽

Heat Stable ◽

Genome Wide ◽

Attractive Therapeutic Target ◽

Heat Stable Protein ◽

Signaling Activation ◽

Shock Proteins

AbstractGlioblastomas (GBM) is the most common primary malignant brain tumor, and radiotherapy plays a critical role in its therapeutic management. Unfortunately, the development of radioresistance is universal. Here, we identified calcium-regulated heat-stable protein 1 (CARHSP1) as a critical driver for radioresistance utilizing genome-wide CRISPR activation screening. This is a protein with a cold-shock domain (CSD)-containing that is highly similar to cold-shock proteins. CARHSP1 mRNA level was upregulated in irradiation-resistant GBM cells and knockdown of CARHSP1 sensitized GBM cells to radiotherapy. The high expression of CARHSP1 upon radiation might mediate radioresistance by activating the inflammatory signaling pathway. More importantly, patients with high levels of CARHSP1 had poorer survival when treated with radiotherapy. Collectively, our findings suggested that targeting the CARHSP1/TNF-α inflammatory signaling activation induced by radiotherapy might directly affect radioresistance and present an attractive therapeutic target for GBM, particularly for patients with high levels of CARHSP1.

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Transcriptional identification of differentially expressed genes during the prepupal–pupal transition in the oriental armyworm, Mythimna separata (Walker) (Lepidoptera: Noctuidae)

Bulletin of Entomological Research ◽

10.1017/s0007485321000171 ◽

2021 ◽

pp. 1-14

Author(s):

Peirong Li ◽

Xinru Li ◽

Wei Wang ◽

Xiaoling Tan ◽

Xiaoqi Wang ◽

...

Keyword(s):

Differentially Expressed Genes ◽

Metabolic Pathways ◽

Developmental Stages ◽

Kegg Pathway ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Mythimna Separata ◽

Kegg Pathway Analysis ◽

Oriental Armyworm ◽

Lepidoptera Noctuidae

Abstract The oriental armyworm, Mythimna separata (Walker) is a serious pest of agriculture that does particular damage to Gramineae crops in Asia, Europe, and Oceania. Metamorphosis is a key developmental stage in insects, although the genes underlying the metamorphic transition in M. separata remain largely unknown. Here, we sequenced the transcriptomes of five stages; mature larvae (ML), wandering (W), and pupation (1, 5, and 10 days after pupation, designated P1, P5, and P10) to identify transition-associated genes. Four libraries were generated, with 22,884, 23,534, 26,643, and 33,238 differentially expressed genes (DEGs) for the ML-vs-W, W-vs-P1, P1-vs-P5, and P5-vs-P10, respectively. Gene ontology enrichment analysis of DEGs showed that genes regulating the biosynthesis of the membrane and integral components of the membrane, which includes the cuticular protein (CP), 20-hydroxyecdysone (20E), and juvenile hormone (JH) biosynthesis, were enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that DEGs were enriched in the metabolic pathways. Of these DEGs, thirty CP, seventeen 20E, and seven JH genes were differentially expressed across the developmental stages. For transcriptome validation, ten CP, 20E, and JH-related genes were selected and verified by real-time PCR quantitative. Collectively, our results provided a basis for further studies of the molecular mechanism of metamorphosis in M. separata.

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Variation in VKORC1 Is Associated with Vascular Dementia

Journal of Alzheimer s Disease ◽

10.3233/jad-201256 ◽

2021 ◽

Vol 80 (3) ◽

pp. 1329-1337

Author(s):

Jure Mur ◽

Daniel L. McCartney ◽

Daniel I. Chasman ◽

Peter M. Visscher ◽

Graciela Muniz-Terrera ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vascular Dementia ◽

Genetic Variant ◽

Warfarin Dose ◽

Uk Biobank ◽

Parental History ◽

Genome Wide ◽

History Of ◽

First Time ◽

The Relationship

Background: The genetic variant rs9923231 (VKORC1) is associated with differences in the coagulation of blood and consequentially with sensitivity to the drug warfarin. Variation in VKORC1 has been linked in a gene-based test to dementia/Alzheimer’s disease in the parents of participants, with suggestive evidence for an association for rs9923231 (p = 1.8×10–7), which was included in the genome-wide significant KAT8 locus. Objective: Our study aimed to investigate whether the relationship between rs9923231 and dementia persists only for certain dementia sub-types, and if those taking warfarin are at greater risk. Methods: We used logistic regression and data from 238,195 participants from UK Biobank to examine the relationship between VKORC1, risk of dementia, and the interplay with warfarin use. Results: Parental history of dementia, APOE variant, atrial fibrillation, diabetes, hypertension, and hypercholesterolemia all had strong associations with vascular dementia (p < 4.6×10–6). The T-allele in rs9923231 was linked to a lower warfarin dose (βperT - allele = –0.29, p < 2×10–16) and risk of vascular dementia (OR = 1.17, p = 0.010), but not other dementia sub-types. However, the risk of vascular dementia was not affected by warfarin use in carriers of the T-allele. Conclusion: Our study reports for the first time an association between rs9923231 and vascular dementia, but further research is warranted to explore potential mechanisms and specify the relationship between rs9923231 and features of vascular dementia.

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Genome-Wide Transcriptomic Analysis of Non-Tumorigenic Tissues Reveals Aging-Related Prognostic Markers and Drug Targets in Renal Cell Carcinoma

Cancers ◽

10.3390/cancers13123045 ◽

2021 ◽

Vol 13 (12) ◽

pp. 3045

Author(s):

Euiyoung Oh ◽

Jun-Hyeong Kim ◽

JungIn Um ◽

Da-Woon Jung ◽

Darren R. Williams ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cancer Patient ◽

Immune Cells ◽

Renal Cell ◽

Prognostic Markers ◽

Patient Survival ◽

Survival Outcome ◽

Normal Tissues ◽

Genome Wide ◽

The Relationship

The relationship between expression of aging-related genes in normal tissues and cancer patient survival has not been assessed. We developed a genome-wide transcriptomic analysis approach for normal tissues adjacent to the tumor to identify aging-related transcripts associated with survival outcome, and applied it to 12 cancer types. As a result, five aging-related genes (DUSP22, MAPK14, MAPKAPK3, STAT1, and VCP) in normal tissues were found to be significantly associated with a worse survival outcome in patients with renal cell carcinoma (RCC). This computational approach was investigated using nontumorigenic immune cells purified from young and aged mice. Aged immune cells showed upregulated expression of all five aging-related genes and promoted RCC invasion compared to young immune cells. Further studies revealed DUSP22 as a regulator and druggable target of metastasis. DUSP22 gene knockdown reduced RCC invasion and the small molecule inhibitor BML-260 prevented RCC dissemination in a tumor/immune cell xenograft model. Overall, these results demonstrate that deciphering the relationship between aging-related gene expression in normal tissues and cancer patient survival can provide new prognostic markers, regulators of tumorigenesis and novel targets for drug development.

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