scholarly journals Comprehensive transcriptional profiling of aging porcine liver

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6949 ◽  
Author(s):  
Jianning Chen ◽  
Qin Zou ◽  
Daojun Lv ◽  
Muhammad Ali Raza ◽  
Xue Wang ◽  
...  
Keyword(s):  
Human Liver ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Genomic Structure ◽  
Circular Rnas ◽  
Transcriptional Level ◽  
Porcine Liver ◽  
Age Related ◽  
Micro Rnas ◽  
Model Animal

Background Aging is a major risk factor for the development of many diseases, and the liver, as the most important metabolic organ, is significantly affected by aging. It has been shown that the liver weight tends to increase in rodents and decrease in humans with age. Pigs have a genomic structure, with physiological as well as biochemical features that are similar to those of humans, and have therefore been used as a valuable model for studying human diseases. The molecular mechanisms of the liver aging of large mammals on a comprehensive transcriptional level remain poorly understood. The pig is an ideal model animal to clearly and fully understand the molecular mechanism underlying human liver aging. Methods In this study, four healthy female Yana pigs (an indigenous Chinese breed) were investigated: two young sows (180-days-old) and two old sows (8-years-old). High throughput RNA sequencing was performed to evaluate the expression profiles of messenger RNA, long non-coding RNAs, micro RNAs, and circular RNAs during the porcine liver aging process. Gene Ontology (GO) analysis was performed to investigate the biological functions of age-related genes. Results A number of age-related genes were identified in the porcine liver. GO annotation showed that up-regulated genes were mainly related to immune response, while the down-regulated genes were mainly related to metabolism. Moreover, several lncRNAs and their target genes were also found to be differentially expressed during liver aging. In addition, the multi-group cooperative control relationships and constructed circRNA-miRNA co-expression networks were assessed during liver aging. Conclusions Numerous age-related genes were identified and circRNA-miRNA co-expression networks that are active during porcine liver aging were constructed. These findings contribute to the understanding of the transcriptional foundations of liver aging and also provide further references that clarify human liver aging at the molecular level.

scholarly journals Circular RNA hsa_circ_0000277 sequesters miR-4766-5p to upregulate LAMA1 and promote esophageal carcinoma progression

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Peng Li Zhou ◽  
Zhengyang Wu ◽  
Wenguang Zhang ◽  
Miao Xu ◽  
Jianzhuang Ren ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Dismal Prognosis ◽  
Advanced Tumor

AbstractGrowing evidence has indicated that circular RNAs (circRNAs) play a pivotal role as functional RNAs in diverse cancers. However, most circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined, and the underlying molecular mechanisms mediated by circRNAs are largely unclear. Here, we screened human circRNA expression profiles in ESCC tissues and found significantly increased expression of hsa_circ_0000277 (termed circPDE3B) in ESCC tissues and cell lines compared to the normal controls. Moreover, higher circPDE3B expression in patients with ESCC was correlated with advanced tumor-node-metastasis (TNM) stage and dismal prognosis. Functional experiments demonstrated that circPDE3B promoted the tumorigenesis and metastasis of ESCC cells in vitro and in vivo. Mechanistically, bioinformatics analysis, a dual-luciferase reporter assay, and anti-AGO2 RNA immunoprecipitation showed that circPDE3B could act as a competing endogenous RNA (ceRNA) by harboring miR-4766-5p to eliminate the inhibitory effect on the target gene laminin α1 (LAMA1). In addition, LAMA1 was significantly upregulated in ESCC tissues and was positively associated with the aggressive oncogenic phenotype. More importantly, rescue experiments revealed that the oncogenic role of circPDE3B in ESCC is partly dependent on the miR-4766-5p/LAMA1 axis. Furthermore, bioinformatics analysis combined with validation experiments showed that epithelial-mesenchymal transition (EMT) activation was involved in the oncogenic functions of the circPDE3B–miR-4766-5p/LAMA1 axis in ESCC. Taken together, we demonstrate for the first time that the circPDE3B/miR-4766-5p/LAMA1 axis functions as an oncogenic factor in promoting ESCC cell proliferation, migration, and invasion by inducing EMT, implying its potential prognostic and therapeutic significance in ESCC.

scholarly journals SMC4, CCNB1 and CKS1B as potential targets and new critical biomarkers for the prognosis of human bladder cancer

2021 ◽  
Author(s):  
Hongpeng Fang ◽  
Zhansen Huang ◽  
Xianzi Zeng ◽  
Jiaming Wan ◽  
Jieying Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Gene Expression Omnibus ◽  
Transcriptional Level ◽  
Hub Genes ◽  
Kaplan Meier ◽  
High Form

Abstract Background As a common malignant cancer of the urinary system, the precise molecular mechanisms of bladder cancer remain to be illuminated. The purpose of this study was to identify core genes with prognostic value as potential oncogenes for the diagnosis, prognosis or novel therapeutic targets of bladder cancer. Methods The gene expression profiles GSE3167 and GSE7476 were available from the Gene Expression Omnibus (GEO) database. Next, PPI network was built to filter the hub gene through the STRING database and Cytoscape software and GEPIA and Kaplan-Meier plotter were implemented. Frequency and type of hub genes and sub groups analysis were performed in cBioportal and ULCAN database. Finally,We used RT-qPCR to confirm our results. Results Totally, 251 DEGs were excavated from two datasets in our study. We only founded high expression of SMC4, TYMS, CCNB1, CKS1B, NUSAP1 and KPNA2 was associated with worse outcomes in bladder cancer patients and no matter from the type of mutation or at the transcriptional level of hub genes, the tumor showed a high form of expression. However, only the expression of SMC4,CCNB1and CKS1B remained changed between the cancer and the normal samples in our results of RT-qPCR. Conclusion In conclusion,These findings indicate that the SMC4,CCNB1 and CKS1B may serve as critical biomarkers in the development and poor prognosis.

scholarly journals Transcriptomic Analysis of mRNA-lncRNA-miRNA Interactions in Hepatocellular Carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Xia Tang ◽  
Delong Feng ◽  
Min Li ◽  
Jinxue Zhou ◽  
Xiaoyuan Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Rna Seq ◽  
Pairwise Interactions ◽  
Micro Rnas ◽  
Non Coding Rnas ◽  
First Time

Abstract Fully elucidating the molecular mechanisms of non-coding RNAs (ncRNAs), including micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs), underlying hepatocarcinogenesis is challenging. We characterized the expression profiles of ncRNAs and constructed a regulatory mRNA-lncRNA-miRNA (MLMI) network based on transcriptome sequencing (RNA-seq) of hepatocellular carcinoma (HCC, n = 9) patients. Of the identified miRNAs (n = 203) and lncRNAs (n = 1,090), we found 16 significantly differentially expressed (DE) miRNAs and three DE lncRNAs. The DE RNAs were highly enriched in 21 functional pathways implicated in HCC (p < 0.05), including p53, MAPK, and NAFLD signaling. Potential pairwise interactions between DE ncRNAs and mRNAs were fully characterized using in silico prediction and experimentally-validated evidence. We for the first time constructed a MLMI network of reciprocal interactions for 16 miRNAs, three lncRNAs, and 253 mRNAs in HCC. The predominant role of MEG3 in the MLMI network was validated by its overexpression in vitro that the expression levels of a proportion of MEG3-targeted miRNAs and mRNAs was changed significantly. Our results suggested that the comprehensive MLMI network synergistically modulated carcinogenesis, and the crosstalk of the network provides a new avenue to accurately describe the molecular mechanisms of hepatocarcinogenesis.

scholarly journals The Mechanism and Clinical Significance of Circular RNAs in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Ziyue Huang ◽  
Haoming Xia ◽  
Shuqiang Liu ◽  
Xudong Zhao ◽  
Risheng He ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Diagnosis ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Clinical Symptoms ◽  
Malignant Tumors ◽  
Research Progress ◽  
Circular Rnas ◽  
Transcriptional Level ◽  
Specificity And Sensitivity

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors worldwide. In view of the lack of early obvious clinical symptoms and related early diagnostic biomarkers with high specificity and sensitivity, most HCC patients are already at the advanced stages at the time of diagnosis, and most of them are accompanied by distant metastasis. Furthermore, the unsatisfactory effect of the follow-up palliative care contributes to the poor overall survival of HCC patients. Therefore, it is urgent to identify effective early diagnosis and prognostic biomarkers and to explore novel therapeutic approaches to improve the prognosis of HCC patients. Circular RNA (CircRNA), a class of plentiful, stable, and highly conserved ncRNA subgroup with the covalent closed loop, is dysregulated in HCC. Increasingly, emerging evidence have confirmed that dysregulated circRNAs can regulate gene expression at the transcriptional or post-transcriptional level, mediating various malignant biological behaviors of HCC cells, including proliferation, invasion, metastasis, immune escape, stemness, and drug resistance, etc.; meanwhile, they are regarded as potential biomarkers for early diagnosis and prognostic evaluation of HCC. This article reviews the research progress of circRNAs in HCC, expounding the potential molecular mechanisms of dysregulated circRNAs in the carcinogenesis and development of HCC, and discusses those application prospects in the diagnosis and prognosis of HCC.

scholarly journals RNA Dynamics in Alzheimer’s Disease

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5113
Author(s):  
Agnieszka Rybak-Wolf ◽  
Mireya Plass
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Neurodegenerative Disorder ◽  
Rna Binding Proteins ◽  
Current Evidence ◽  
Circular Rnas ◽  
Rna Dynamics ◽  
Age Related

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder that heavily burdens healthcare systems worldwide. There is a significant requirement to understand the still unknown molecular mechanisms underlying AD. Current evidence shows that two of the major features of AD are transcriptome dysregulation and altered function of RNA binding proteins (RBPs), both of which lead to changes in the expression of different RNA species, including microRNAs (miRNAs), circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs). In this review, we will conduct a comprehensive overview of how RNA dynamics are altered in AD and how this leads to the differential expression of both short and long RNA species. We will describe how RBP expression and function are altered in AD and how this impacts the expression of different RNA species. Furthermore, we will also show how changes in the abundance of specific RNA species are linked to the pathology of AD.

scholarly journals Constructing mRNA, miRNA, circRNA and lncRNA Regulatory Network by Analysis of Microarray data in Breast Cancer

2021 ◽  
Author(s):  
Bita Hassani ◽  
Hasan Mollanoori ◽  
Farkhondeh Pouresmaeili ◽  
Yazdan Asgari ◽  
Soudeh Ghafouri-Fard
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Noncoding Rnas ◽  
Interaction Network ◽  
Gene Expression Omnibus ◽  
Good Prognosis ◽  
Therapeutic Options ◽  
Circular Rnas ◽  
Breast Tumorigenesis

Abstract Background. Luminal tumors are the utmost frequent subtype of breast cancer (BC). Despite luminal BC has relatively good prognosis, in a subset of patients, disease relapse occursto endocrine therapy ;hence, there is a critical need to identify new strategies to promote the early detection and more effective therapies. Noncoding RNAs including microRNAs, long noncoding RNAs, and circular RNAs can interact with and modulate each other via diverse molecular mechanisms and make a complicated regulatory network.ncRNAs participate in diverse biological processes and disorders such as breast tumors. Therefore, understanding their regulatory mechanisms allow to develop new field of research and therapeutic options for BC patients.Methods. In this study, BC-specific RNA expression profiles including mRNAs, miRNAs, lncRNAs, and circRNAs were retrievedfrom Gene Expression Omnibus microarray datasets, and differentially expressed(DE) items were obtained. Disease ontology, functional and pathway enrichment analyses were executed. The protein-protein interaction network was constructed, and hub mRNAs were extracted.The prognostic value of hub mRNAs in patients of BC were performed. Subsequently, a ceRNA network was established.Results. In total, 691 DE genes, 122 DE lncRNAs, 60 DE miRNAs, and 38 DE circRNAs in breast tumor samples were compared with normal samples. Subsequently, 12 hub-genesincluding FOXO3, RHOA, EZH2, KIT, HSP90B1, NCOA3, RAC1, IGF1, CAV1, CXCR4, CCNB1, and ITGB1 were screened from the network. Kaplan-Meier Plotter results revealed that FOXO3 and RHOA were a suitable prognostic marker for patients with breast cancer. Finally, we determined possible ncRNAs (circ0007535, circ0002727, circ0005240, circ0014130, circ0044927, circ0007001, circ0089153,NORAD, MALAT1, TUG1, ZFAS1, OPI5-AS1, miR183,miR182, miR101, miR200c, miR200b, miR149, miR342, and miR1207) which could crosstalk with each other to regulateFOXO3 and RHOA through different regulatory patterns. Conclusion. These data might improve our perception of the breast tumorigenesis and could develop new field of research and therapeutic options for BC patients.

Identification and Characterization of Rice Circular RNAs Responding to Xanthomonas Oryzae pv. Oryzae Invasion

2021 ◽  
Author(s):  
Peihong Wang ◽  
Sai Wang ◽  
Yan Wu ◽  
Wenhan Nie ◽  
Ayizekeranmu Yiming ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Circular Rnas ◽  
Pathogen Invasion ◽  
Rice Leaves ◽  
Transcriptional Gene Regulation ◽  
Identification And Characterization ◽  
Host Genes

Abstract BackgroundThe emerging role of circular RNAs (circRNAs) in various biological processes have advanced our knowledge of transcriptional and post-transcriptional gene regulation. The number and expression of plant circRNAs vary with species and treatments. However, the expression profile and the potential role of circRNAs during plant response to pathogen invasion are still elusive. ResultsIn this study, we identified 3517 circRNAs from PXO99A-infected rice leaves using the ribosomal RNA (rRNA) depleted RNA-Sequencing technique coupled with the CIRI2 and CIRCexplorer2 pipeline. Among them, 2994 (85.13%) circRNAs arised from the exons of their parent genes, 1214 circRNAs were previously unknown and 276 circRNAs exhibited differential expression profiles upon PXO99A infection over time. In addition, 31 differentially expressed circRNAs (DEcircRNAs) were predicted as the corresponding 121 miRNAs sponges. Functional analysis of both host genes and target mRNAs suggested that these identified circRNAs might play an important role in reprogramming rice responses to PXO99A invasion, mainly by mediating photorespiration, chloroplast, peroxisome and diterpenoid biosynthesis associated pathways.ConclusionThese results inferred a potential functional role of circRNAs in the regulation of rice immunity and provide novel clues for revealing the molecular mechanisms of rice-PXO99A interaction.

scholarly journals Exosomes and Micro-RNAs in Aging Process

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 968
Author(s):  
Yousra Hamdan ◽  
Loubna Mazini ◽  
Gabriel Malka
Keyword(s):  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Biological Fluids ◽  
Cell Types ◽  
Exosome Biogenesis ◽  
Age Related ◽  
Micro Rnas ◽  
Underlying Mechanisms ◽  
Almost All

Exosomes are the main actors of intercellular communications and have gained great interest in the new cell-free regenerative medicine. These nanoparticles are secreted by almost all cell types and contain lipids, cytokines, growth factors, messenger RNA, and different non-coding RNA, especially micro-RNAs (mi-RNAs). Exosomes’ cargo is released in the neighboring microenvironment but is also expected to act on distant tissues or organs. Different biological processes such as cell development, growth and repair, senescence, migration, immunomodulation, and aging, among others, are mediated by exosomes and principally exosome-derived mi-RNAs. Moreover, their therapeutic potential has been proved and reinforced by their use as biomarkers for disease diagnostics and progression. Evidence has increasingly shown that exosome-derived mi-RNAs are key regulators of age-related diseases, and their involvement in longevity is becoming a promising issue. For instance, mi-RNAs such as mi-RNA-21, mi-RNA-29, and mi-RNA-34 modulate tissue functionality and regeneration by targeting different tissues and involving different pathways but might also interfere with long life expectancy. Human mi-RNAs profiling is effectively related to the biological fluids that are reported differently between young and old individuals. However, their underlying mechanisms modulating cell senescence and aging are still not fully understood, and little was reported on the involvement of mi-RNAs in cell or tissue longevity. In this review, we summarize exosome biogenesis and mi-RNA synthesis and loading mechanism into exosomes’ cargo. Additionally, we highlight the molecular mechanisms of exosomes and exosome-derived mi-RNA regulation in the different aging processes.

scholarly journals Comprehensive Characterization of Androgen-Responsive circRNAs in Prostate Cancer

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1096
Author(s):  
Zhe Kong ◽  
Yali Lu ◽  
Xuechao Wan ◽  
Jun Luo ◽  
Dujian Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Circular Rnas ◽  
Transcriptional Level ◽  
The Novel ◽  
Cancer Tissues ◽  
Posttranscriptional Level

The androgen receptor (AR) signaling pathway plays an important role in the initiation and progression of prostate cancer. Circular RNAs (circRNAs), the novel noncoding RNAs without 5′ to 3′ polarity or 3′ poly (A), play an important role in multiple diseases. However, the potential roles of androgen-responsive circRNAs in prostate cancer remain unclear. In this study, we identified 3237 androgen-responsive circRNAs and 1954 androgen-responsive mRNAs after dihydrotestosterone (DHT) stimulation using microarray. Among them, the expression of 1296 androgen-responsive circRNAs was consistent with that of their parent genes, and we thought AR might regulate the expression of these circRNAs at the transcriptional level. In addition, 1941 circRNAs expression was not consistent with their parent genes, and we speculated that AR may regulate the expression of those circRNAs at the posttranscriptional level through affecting alternative splicing. Analyzing the androgen-responsive circRNAs regulated at the posttranscriptional level, we identified two key RNA binding proteins (RBPs), WTAP and TNRC6, using the circInteractome database, which may play important role in the biogenesis of androgen-responsive circRNAs. Furthermore, we explored the potential biological functions and predicted the molecular mechanisms of two dysregulated circRNAs (circNFIA and circZNF561) in prostate cancer. In this study, we revealed that circNFIA was upregulated in prostate cancer tissues and plasma samples from patients with prostate cancer; circNFIA may play an oncogenic role in prostate cancer. In contrast, circZNF561 was downregulated and may act as a tumor suppressor in prostate cancer. Our results suggest that androgen-responsive circRNAs might regulate the progression of prostate cancer and could be novel diagnostic biomarkers.

scholarly journals Constructing MRNA, miRNA, circRNA and lncRNA Regulatory Network by Analysis of Microarray Data in Breast Cancer

2021 ◽  
Author(s):  
Bita Hassani ◽  
Hasan Mollanoori ◽  
Farkhondeh Pouresmaeili ◽  
Yazdan Asgari ◽  
Soudeh Ghafouri-Fard
Keyword(s):  
Breast Cancer ◽  
Regulatory Network ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Noncoding Rnas ◽  
Interaction Network ◽  
Good Prognosis ◽  
Therapeutic Options ◽  
Circular Rnas ◽  
Breast Tumorigenesis

Abstract Background. Luminal tumors are the utmost frequent subtype of breast cancer (BC). Despite luminal BC has relatively good prognosis, in a subset of patients, disease relapse occurs to endocrine therapy ;hence, there is a critical need to identify new strategies to promote the early detection and more effective therapies. Noncoding RNAs including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) can interact with and modulate each other via diverse molecular mechanisms and make a complicated regulatory network. ncRNAs participate in diverse biological processes and disorders such as breast tumors. Therefore, understanding their regulatory mechanisms allow to develop new field of research and therapeutic options for BC patients. Methods. In this study, BC-specific RNA expression profiles including mRNAs, miRNAs, lncRNAs, and circRNAs were retrieved from Gene Expression Omnibus (GEO) microarray datasets, and differentially expressed (DE) items were obtained. Disease ontology, functional and pathway enrichment analyses were executed. The protein-protein interaction network was constructed, and hub mRNAs were extracted. The prognostic value of hub mRNAs in patients of BC were performed using GEPIA. Subsequently, a ceRNA network was established by Cytoscape.Results. In total, 691 DE genes, 122 DE lncRNAs, 60 DE miRNAs, and 38 DE circRNAs in breast tumor samples were compared with normal samples. Subsequently, 12 hub-genes including FOXO3, RHOA, EZH2, KIT, HSP90B1, NCOA3, RAC1, IGF1, CAV1, CXCR4, CCNB1, and ITGB1 were screened from the network. Kaplan-Meier Plotter results revealed that FOXO3 and RHOA were a suitable prognostic marker for patients with breast cancer. Finally, we determined possible ncRNAs (circ0007535, circ0002727, circ0005240, circ0014130, circ0044927, circ0007001, circ0089153, NORAD, MALAT1, TUG1, ZFAS1, OPI5-AS1, miR183, miR182, miR101, miR200c, miR200b, miR149, miR342, and miR1207) which could crosstalk with each other to regulate FOXO3 and RHOA through different regulatory patterns. Conclusion. These data might improve our perception of the breast tumorigenesis and could develop new field of research and therapeutic options for BC patients.

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