scholarly journals Transcriptome Analysis of Long Noncoding RNAs in Toll-Like Receptor 3-Activated Mesenchymal Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Shihua Wang ◽  
Xiaoxia Li ◽  
Robert Chunhua Zhao

Mesenchymal stem cells (MSCs) possess great immunomodulatory capacity which lays the foundation for their therapeutic effects in a variety of diseases. Recently, toll-like receptors (TLR) have been shown to modulate MSC functions; however, the underlying molecular mechanisms are poorly understood. Emerging evidence suggests that long noncoding RNAs (lncRNAs) are an important class of regulators involved in a wide range of biological processes. To explore the potential involvement of lncRNAs in TLR stimulated MSCs, we performed a comprehensive lncRNA and mRNA profiling through microarray. 10.2% of lncRNAs (1733 out of 16967) and 15.1% of mRNA transcripts (1760 out of 11632) were significantly differentially expressed (absolute fold-change≥5 ,Pvalue≤0.05) in TLR3 stimulated MSCs. Furthermore, we characterized the differentially expressed lncRNAs through their classes and length distribution and correlated them with differentially expressed mRNA. Here, we are the first to determine genome-wide lncRNAs expression patterns in TLR3 stimulated MSCs by microarray and this work could provide a comprehensive framework of the transcriptome landscapes of TLR3 stimulated MSCs.

2018 ◽  
Vol 243 (13) ◽  
pp. 1074-1082 ◽  
Author(s):  
Xiujun Li ◽  
Jiali Wang ◽  
Yuchen Pan ◽  
Yujun Xu ◽  
Dan Liu ◽  
...  

Further studies on the molecular mechanisms of mesenchymal stem cells in the maintenance of growth and function are essential for their clinical application. Growing evidence has shown that long non-coding RNAs (lncRNAs) play an important role in the regulation of mesenchymal stem cells. Recently, it is reported that highly upregulated in liver cancer (HULC), with another lncRNA MALAT-1, accelerated liver cancer stem cell growth. The regulating role of MALAT-1 in mesenchymal stem cells has been investigated. However, the effects of HULC on the mesenchymal stem cells are unknown. In this study, we overexpressed HULC in mesenchymal stem cells derived from umbilical cord and analyzed the cell phenotypes, proliferation, apoptosis, migration, invasion and differentiation of mesenchymal stem cells. We found that overexpression of HULC significantly promotes cell proliferation through promoting cell division and inhibits cell apoptosis. HULC-overexpressed mesenchymal stem cells migrate and invade faster than control mesenchymal stem cells. HULC has no effect on phenotypes and differentiation of mesenchymal stem cells. Furthermore, we found that the expression of HULC in mesenchymal stem cells could be reduced by several inflammatory factors, including TNF-α, TGF-β1, and R848. Taken together, our data demonstrated that HULC has a vital role in the growth and function maintenance of mesenchymal stem cells without affecting differentiation. Impact statement Exploring the molecular mechanisms of growth and function in MSCs is the key to improve their clinical therapeutic effects. Currently, more and more evidence show that the long non-coding RNA (lncRNA) plays an important role in the growth, stemness and function of MSCs.Both HULC and MALAT1 are the earliest discovered LNCRNAs, which are closely related to tumor growth. All of them can promote the growth of liver cancer stem cells. Previously, we have studied the effects of MALAT1 on the growth and function of MSCs. In this study, we focused on the effects of HULC on MSCs. We elucidated the effects of HULC on the growth and differentiation of MSCs, and explored the relationship between inflammatory stimuli and HULC expression in MSCs. Our findings provide a new molecular target for the growth and clinical application of MSCs.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Fuchun Fang ◽  
Kaiying Zhang ◽  
Zhao Chen ◽  
Buling Wu

Abstract Odontoblasts are cells that contribute to the formation of the dental pulp complex. The differentiation of dental tissue-derived mesenchymal stem cells into odontoblasts comprises many factors and signaling pathways. Noncoding RNAs (ncRNAs), comprising a substantial part of poly-A tail mature RNAs, are considered “transcriptional noise.” Emerging evidence has shown that ncRNAs have key functions in the differentiation of mesenchymal stem cells. In this review, we discussed two major types of ncRNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), in terms of their role in the odontogenic differentiation of dental tissue-derived stem cells. Recent findings have demonstrated important functions for miRNAs and lncRNAs in odontogenic differentiation. It is expected that ncRNAs will become promising therapeutic targets for dentin regeneration based on stem cells.


2018 ◽  
Vol 14 (3) ◽  
pp. 297-308 ◽  
Author(s):  
Qiaolin Yang ◽  
Lingfei Jia ◽  
Xiaobei Li ◽  
Runzhi Guo ◽  
Yiping Huang ◽  
...  

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yaqiong Wu ◽  
Jing Guo ◽  
Tongli Wang ◽  
Fuliang Cao ◽  
Guibin Wang

Abstract Background Long noncoding RNAs (lncRNAs) play an important role in diverse biological processes and have been widely studied in recent years. However, the roles of lncRNAs in leaf pigment formation in ginkgo (Ginkgo biloba L.) remain poorly understood. Results In this study, lncRNA libraries for mutant yellow-leaf and normal green-leaf ginkgo trees were constructed via high-throughput sequencing. A total of 2044 lncRNAs were obtained with an average length of 702 nt and typically harbored 2 exons. We identified 238 differentially expressed lncRNAs (DELs), 32 DELs and 49 differentially expressed mRNAs (DEGs) that constituted coexpression networks. We also found that 48 cis-acting DELs regulated 72 target genes, and 31 trans-acting DELs regulated 31 different target genes, which provides a new perspective for the regulation of the leaf-color mutation. Due to the crucial regulatory roles of lncRNAs in a wide range of biological processes, we conducted in-depth studies on the DELs and their targets and found that the chloroplast thylakoid membrane subcategory and the photosynthesis pathways (ko00195) were most enriched, suggesting their potential roles in leaf coloration mechanisms. In addition, our correlation analysis indicates that eight DELs and 68 transcription factors (TFs) might be involved in interaction networks. Conclusions This study has enriched the knowledge concerning lncRNAs and provides new insights into the function of lncRNAs in leaf-color mutations, which will benefit future selective breeding of ginkgo.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Liang Guo ◽  
Kai Xu ◽  
Hongbo Yan ◽  
Haifeng Feng ◽  
Linlin Chai ◽  
...  

Background. Long noncoding RNAs (lncRNAs) play key roles in a wide range of biological processes and their deregulation results in human disease, including keloids. Earlobe keloid is a type of pathological skin scar, and the molecular pathogenesis of this disease remains largely unknown. Methods. In this study, microarray analysis was used to determine the expression profiles of lncRNAs and mRNAs between 3 pairs of earlobe keloid and normal specimens. Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to identify the main functions of the differentially expressed genes and earlobe keloid-related pathways. Results. A total of 2068 lncRNAs and 1511 mRNAs were differentially expressed between earlobe keloid and normal tissues. Among them, 1290 lncRNAs and 1092 mRNAs were upregulated, and 778 lncRNAs and 419 mRNAs were downregulated. Pathway analysis revealed that 24 pathways were correlated to the upregulated transcripts, while 11 pathways were associated with the downregulated transcripts. Conclusion. We characterized the expression profiles of lncRNA and mRNA in earlobe keloids and suggest that lncRNAs may serve as diagnostic biomarkers for the therapy of earlobe keloid.


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Minqiu Lu ◽  
Ying Hu ◽  
Yin Wu ◽  
Huixing Zhou ◽  
Yuan Jian ◽  
...  

Abstract Background Long noncoding RNAs (lncRNAs) are involved in a wide range of biological processes in tumorigenesis. However, the role of lncRNA expression in the biology, prognosis, and molecular classification of human multiple myeloma (MM) remains unclear, especially the biological functions of the vast majority of lncRNAs. Recently, lncRNAs have been identified in neoplastic hematologic disorders. Evidence has accumulated on the molecular mechanisms of action of lncRNAs, providing insight into their functional roles in tumorigenesis. This study aimed to characterize potential lncRNAs in patients with MM. Methods In this study, the whole-transcriptome strand-specific RNA sequencing of samples from three newly diagnosed patients with MM was performed. The whole transcriptome, including lncRNAs, microRNAs, and mRNAs, was analyzed. Using these data, MM lncRNAs were systematically analyzed, and the lncRNAs involved in the occurrence of MM were identified. Results The results revealed that MM lncRNAs had distinctive characteristics different from those of other malignant tumors. Further, the functions of a set of lncRNAs preferentially expressed in MM were verified, and several lncRNAs were identified as competing endogenous RNAs. More importantly, the aberrant expression of certain lncRNAs, including maternally expressed gene3, colon cancer–associated transcript1, and coiled-coil domain-containing 26, as well as some novel lncRNAs involved in the occurrence of MM was established. Further, lncRNAs were related to some microRNAs, regulated each other, and participated in MM development. Conclusions Genome-wide screening and functional analysis enabled the identification of a set of lncRNAs involved in the occurrence of MM. The interaction exists among microRNAs and lncRNAs.


2019 ◽  
Vol 2019 ◽  
pp. 1-16
Author(s):  
Fei Liu ◽  
Jiazhang Wei ◽  
Yanrong Hao ◽  
Fengzhu Tang ◽  
Wei Jiao ◽  
...  

Our previous studies showed that ZBTB7A played an important role in promoting nasopharyngeal carcinoma (NPC) progression. However, molecular mechanisms of different levels of ZBTB7A are still unclear. It is necessary to search molecular markers which are closely connected with ZBTB7A. We selected NPC sublines CNE2 with stably transfecting empty plasmid (negative control, NC) and short hair RNA (shRNA) plasmid targeting ZBTB7A as research objectives. Microarray was used to screen differentially expressed long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) via shRNA-CNE2 versus NC-CNE2. Quantitative PCR (qPCR) was used to validate lncRNAs and mRNAs from the sublines, chronic rhinitis, and NPC tissues. Bioinformatics was used to analyze regulatory pathways which were connected with ZBTB7A. The 1501 lncRNAs (long noncoding RNAs) and 1275 differentially expressed mRNAs were upregulated or downregulated over 2-fold. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the upregulated or downregulated carbohydrate and lipid metabolisms probably involved in carcinogenicity of shRNA-CNE2 (P-value cut-off was 0.05). In order to find the molecular mechanisms of ZBTB7A, we validated 12 differentially expressed lncRNAs and their nearby mRNAs by qPCR. Most of the differentially expressed mRNAs are closely connected with carbohydrate and lipid metabolisms in multiply cancers. Furthermore, part of them were validated in NPC and rhinitis tissues by qPCR. As a result, NR_047538, ENST00000442852, and fatty acid synthase (FASN) were closely associated with NPC. ZBTB7A had a positive association with NR_047538 and negative associations with ENST00000442852 and FASN. The results probably provide novel candidate biomarkers for NPC progression with different levels of ZBTB7A.


2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Lu-Mei Chi ◽  
Li-Ping Wang ◽  
Dan Jiao

Objectives. This study aims to determine differentially expressed genes (DEGs) and long noncoding RNAs (lncRNAs) associated with Parkinson’s disease (PD) using a microarray. Methods. We downloaded the microarray data GSE6613 from the Gene Expression Omnibus, which included 105 samples. We selected 72 samples comprising 22 healthy control blood samples and 50 PD blood samples for further analysis. Later, we used Limma to screen DEGs and differentially expressed lncRNAs (DElncRNAs) and estimated their functions by the Gene Ontology (GO). Besides, the competing endogenous RNA (ceRNA) network, including microRNAs, lncRNAs, and mRNAs, was constructed to elucidate the regulatory mechanism. Furthermore, we performed the KEGG pathway enrichment with mRNAs in the ceRNA regulatory network and constructed a final network, including pathways, mRNAs, microRNAs, and lncRNAs. Results. Overall, we obtained 394 DEGs, including 207 upregulated DEGs and 187 downregulated DEGs, and 7 DElncRNAs, including 2 upregulated DElncRNAs and 5 downregulated DElncRNAs. Insulin-like growth factor-1 receptor (IGF1R) was considerably enriched in the endocytosis pathway. In the ceRNA regulation network, IGF1R was the target of hsa-miR-133b and lncRNAs of XIST, and PART1 could also be the target of hsa-miR-133b. While the upregulated DEGs were enriched in the GO terms of the cytoskeleton, cytoskeletal part, and microtubule cytoskeleton, the downregulated DEGs were enriched in the immune response. PRKACA was markedly enriched in numerous pathways, including the MAPK and insulin signaling pathways. Conclusions. IGF1R, PRKACA, and lncRNA-XIST could be potentially involved in PD, and these diverse molecular mechanisms could support the development of the similar treatment for PD.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1787
Author(s):  
Ebtehal Ahmed ◽  
Tarek Saleh ◽  
Meifeng Xu

The functionalization of decellularized scaffolds is still challenging because of the recellularization-related limitations, including the finding of the most optimal kind of cell(s) and the best way to control their distribution within the scaffolds to generate native mimicking tissues. That is why researchers have been encouraged to study stem cells, in particular, mesenchymal stem cells (MSCs), as alternative cells to repopulate and functionalize the scaffolds properly. MSCs could be obtained from various sources and have therapeutic effects on a wide range of inflammatory/degenerative diseases. Therefore, in this mini-review, we will discuss the benefits using of MSCs for recellularization, the factors affecting their efficiency, and the drawbacks that may need to be overcome to generate bioengineered transplantable organs.


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