scholarly journals H19, a Long Non-coding RNA, Mediates Transcription Factors and Target Genes through Interference of MicroRNAs in Pan-Cancer

2020 ◽  
Vol 21 ◽  
pp. 180-191 ◽  
Author(s):  
Aimin Li ◽  
Saurav Mallik ◽  
Haidan Luo ◽  
Peilin Jia ◽  
Dung-Fang Lee ◽  
...  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guoning Wang ◽  
Xingfen Wang ◽  
Yan Zhang ◽  
Jun Yang ◽  
Zhikun Li ◽  
...  

Abstract Background Verticillium wilt is a widespread and destructive disease, which causes serious loss of cotton yield and quality. Long non-coding RNA (lncRNA) is involved in many biological processes, such as plant disease resistance response, through a variety of regulatory mechanisms, but their possible roles in cotton against Verticillium dahliae infection remain largely unclear. Results Here, we measured the transcriptome of resistant G. hirsutum following infection by V. dahliae and 4277 differentially expressed lncRNAs (delncRNAs) were identified. Localization and abundance analysis revealed that delncRNAs were biased distribution on chromosomes. We explored the dynamic characteristics of disease resistance related lncRNAs in chromosome distribution, induced expression profiles, biological function, and these lncRNAs were divided into three categories according to their induced expression profiles. For the delncRNAs, 687 cis-acting pairs and 14,600 trans-acting pairs of lncRNA-mRNA were identified, which indicated that trans-acting was the main way of Verticillium wilt resistance-associated lncRNAs regulating target mRNAs in cotton. Analyzing the regulation pattern of delncRNAs revealed that cis-acting and trans-acting lncRNAs had different ways to influence target genes. Gene Ontology (GO) enrichment analysis revealed that the regulatory function of delncRNAs participated significantly in stimulus response process, kinase activity and plasma membrane components. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that delncRNAs participated in some important disease resistance pathways, such as plant-pathogen interaction, alpha-linolenic acid metabolism and plant hormone signal transduction. Additionally, 21 delncRNAs and 10 target genes were identified as being involved in alpha-linolenic acid metabolism associated with the biosynthesis of jasmonic acid (JA). Subsequently, we found that GhlncLOX3 might regulate resistance to V. dahliae through modulating the expression of GhLOX3 implicated in JA biosynthesis. Further functional analysis showed that GhlncLOX3-silenced seedlings displayed a reduced resistance to V. dahliae, with down-regulated expression of GhLOX3 and decreased content of JA. Conclusion This study shows the dynamic characteristics of delncRNAs in multiaspect, and suggests that GhlncLOX3-GhLOX3-JA network participates in response to V. dahliae invasion. Our results provide novel insights for genetic improvement of Verticillium wilt resistance in cotton using lncRNAs.


2021 ◽  
Vol 22 (15) ◽  
pp. 8088
Author(s):  
Tan Phát Pham ◽  
Anke S. van Bergen ◽  
Veerle Kremer ◽  
Simone F. Glaser ◽  
Stefanie Dimmeler ◽  
...  

Endothelial cells can acquire a mesenchymal phenotype through a process called Endothelial-to-Mesenchymal transition (EndMT). This event is found in embryonic development, but also in pathological conditions. Blood vessels lose their ability to maintain vascular homeostasis and ultimately develop atherosclerosis, pulmonary hypertension, or fibrosis. An increase in inflammatory signals causes an upregulation of EndMT transcription factors, mesenchymal markers, and a decrease in endothelial markers. In our study, we show that the induction of EndMT results in an increase in long non-coding RNA AERRIE expression. JMJD2B, a known EndMT regulator, induces AERRIE and subsequently SULF1. Silencing of AERRIE shows a partial regulation of SULF1 but showed no effect on the endothelial and mesenchymal markers. Additionally, the overexpression of AERRIE results in no significant changes in EndMT markers, suggesting that AERRIE is marginally regulating mesenchymal markers and transcription factors. This study identifies AERRIE as a novel factor in EndMT, but its mechanism of action still needs to be elucidated.


Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 2006
Author(s):  
Hongyu Liu ◽  
Ibrar Muhammad Khan ◽  
Huiqun Yin ◽  
Xinqi Zhou ◽  
Muhammad Rizwan ◽  
...  

The mRNAs and long non-coding RNAs axes are playing a vital role in the regulating of post-transcriptional gene expression. Thereby, elucidating the expression pattern of mRNAs and long non-coding RNAs underlying testis development is crucial. In this study, mRNA and long non-coding RNAs expression profiles were investigated in 3-month-old calves and 3-year-old mature bulls’ testes by total RNA sequencing. Additionally, during the gene level analysis, 21,250 mRNAs and 20,533 long non-coding RNAs were identified. As a result, 7908 long non-coding RNAs (p-adjust < 0.05) and 5122 mRNAs (p-adjust < 0.05) were significantly differentially expressed between the distinct age groups. In addition, gene ontology and biological pathway analyses revealed that the predicted target genes are enriched in the lysine degradation, cell cycle, propanoate metabolism, adherens junction and cell adhesion molecules pathways. Correspondingly, the RT-qPCR validation results showed a strong consistency with the sequencing data. The source genes for the mRNAs (CCDC83, DMRTC2, HSPA2, IQCG, PACRG, SPO11, EHHADH, SPP1, NSD2 and ACTN4) and the long non-coding RNAs (COX7A2, COX6B2, TRIM37, PRM2, INHBA, ERBB4, SDHA, ATP6VOA2, FGF9 and TCF21) were found to be actively associated with bull sexual maturity and spermatogenesis. This study provided a comprehensive catalog of long non-coding RNAs in the bovine testes and also offered useful resources for understanding the differences in sexual development caused by the changes in the mRNA and long non-coding RNA interaction expressions between the immature and mature stages.


2018 ◽  
Vol 19 (11) ◽  
pp. 3610 ◽  
Author(s):  
Eveline Ibeagha-Awemu ◽  
Ran Li ◽  
Pier-Luc Dudemaine ◽  
Duy Do ◽  
Nathalie Bissonnette

This study aimed to characterize the long non-coding RNA (lncRNA) expression in the bovine mammary gland and to infer their functions in dietary response to 5% linseed oil (LSO) or 5% safflower oil (SFO). Twelve cows (six per treatment) in mid lactation were fed a control diet for 28 days followed by a treatment period (control diet supplemented with 5% LSO or 5% SFO) of 28 days. Mammary gland biopsies were collected from each animal on day-14 (D-14, control period), D+7 (early treatment period) and D+28 (late treatment period) and were subjected to RNA-Sequencing and subsequent bioinformatics analyses. Functional enrichment of lncRNA was performed via potential cis regulated target genes located within 50 kb flanking regions of lncRNAs and having expression correlation of >0.7 with mRNAs. A total of 4955 lncRNAs (325 known and 4630 novel) were identified which potentially cis targeted 59 and 494 genes in LSO and SFO treatments, respectively. Enrichments of cis target genes of lncRNAs indicated potential roles of lncRNAs in immune function, nucleic acid metabolism and cell membrane organization processes as well as involvement in Notch, cAMP and TGF-β signaling pathways. Thirty-two and 21 lncRNAs were differentially expressed (DE) in LSO and SFO treatments, respectively. Six genes (KCNF1, STARD13, BCL6, NXPE2, HHIPL2 and MMD) were identified as potential cis target genes of six DE lncRNAs. In conclusion, this study has identified lncRNAs with potential roles in mammary gland functions and potential candidate genes and pathways via which lncRNAs might function in response to LSO and SFA.


2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Ying Wang ◽  
Chenyi Xue ◽  
Muredach Reilly ◽  
Hanrui Zhang

We aim to interrogate the functions of a subset of human macrophage intergenic long non-coding RNA (lincRNAs) which harbor cardiometabolic trait-associated single nucleotide polymorphisms (SNPs). We have found that one lincRNA RP11-472N13.3 overlaps rs7081678, a SNP significantly associated with central obesity (WHRadjBMI; P =5.57x10 -6 ). RP11-472N13.3 expression is enriched in macrophages relative to other obesity relevant tissues. Thus, RP11-472N13.3 SNPs for obesity may act via its myeloid cell modulation in adipose. In human monocyte-derived macrophage (HMDM), human induced pluripotent stem cell-derived macrophages (IPSDM) and THP1-derived macrophages (THP-1Φ), at RNAseq and Q-PCR, RP11-472N13.3 is abundant in M0 and M2(IL-4) macrophages but markedly suppressed in the M1 state (LPS/IFNγ). RP11-472N13.3 localizes almost exclusively to the cytoplasmic fraction of M0-HMDM. Consistent with GENCODE, our HMDM RNAseq data suggest a single 2-exon isoform. ChIP-seq reveals PU.1 and C/EBP-β binding at RP11-472N13.3 transcription start site. In our HMDM RNAseq (n=30 subjects) data, RP11-472N13.3 expression was inversely correlated with IFNγ-JAK-STAT signaling genes (e.g., IRF4, IL-12A, IL-23, STAT1, SOCS1, SOCS3 ), but not LPS/TLR4 activated genes (e.g., TNFA, CXCL9, CXCL10, IL1B ). Furthermore, KD of RP11-472N13.3 using siRNA or LNA-ASO in THP-1Φ, amplified expression of IFNγ target genes but not LPS/TLR4 targets during M1 activation (LPS/IFNγ). These data suggest its potential role in modulating IFNγ signaling. Mechanistic studies are needed to examine the molecular mechanisms.


Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1374
Author(s):  
Yibing Liu ◽  
Ying Yu ◽  
Hong Ao ◽  
Fengxia Zhang ◽  
Xitong Zhao ◽  
...  

Adipose is an important body tissue in pigs, and fatty traits are critical in pig production. The function of long non-coding RNA (lncRNA) in fat deposition and metabolism has been found in previous studies. In this study, we collected the adipose tissue of six Landrace pigs with contrast backfat thickness (nhigh = 3, nlow = 3), after which we performed strand-specific RNA sequencing (RNA-seq) based on pooling and biological replicate methods. Biological replicate and pooling RNA-seq revealed 1870 and 1618 lncRNAs, respectively. Using edgeR, we determined that 1512 genes and 220 lncRNAs, 2240 genes and 127 lncRNAs were differentially expressed in biological replicate and pooling RNA-seq, respectively. After target gene prediction, we found that ACSL3 was cis-targeted by lncRNA TCONS-00052400 and could activate the conversion of long-chain fatty acids. In addition, lncRNA TCONS_00041740 cis-regulated gene ACACB regulated the rate-limiting enzyme in fatty acid oxidation. Since these genes have necessary functions in fat metabolism, the results imply that the lncRNAs detected in our study may affect backfat deposition in swine through regulation of their target genes. Our study explored the regulation of lncRNA and their target genes in porcine backfat deposition and provided new insights for further investigation of the biological functions of lncRNA.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaobin Luo ◽  
Tianqi Tu ◽  
Yali Zhong ◽  
Shangyi Xu ◽  
Xiangzhou Chen ◽  
...  

Glioblastoma accounts for 45.2% of central nervous system tumors. Despite the availability of multiple treatments (e.g., surgery, radiotherapy, chemotherapy, biological therapy, immunotherapy, and electric field therapy), glioblastoma has a poor prognosis, with a 5-year survival rate of approximately 5%. The pathogenesis and prognostic markers of this cancer are currently unclear. To this end, this study aimed to explore the pathogenesis of glioblastoma and identify potential prognostic markers. We used data from the GEO and TCGA databases and identified five genes (ITGA5, MMP9, PTPRN, PTX3, and STX1A) that could affect the survival rate of glioblastoma patients and that were differentially expressed between glioblastoma patients and non-tumors groups. Based on a variety of bioinformatics tools for reverse prediction of target genes associated with the prognosis of GBM, a ceRNA network of messenger RNA (STX1A, PTX3, MMP9)-microRNA (miR-9-5p)-long non-coding RNA (CRNDE) was constructed. Finally, we identified five potential therapeutic drugs (bacitracin, hecogenin, clemizole, chrysin, and gibberellic acid) that may be effective treatments for glioblastoma.


Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 157 ◽  
Author(s):  
Jian Zheng ◽  
Zhibo Wang ◽  
Hua Yang ◽  
Xiaolei Yao ◽  
Pengcheng Yang ◽  
...  

Long non-coding RNA (LncRNA) have been identified as important regulators in the hypothalamic-pituitary-ovarian axis associated with sheep prolificacy. However, their expression pattern and potential roles in the pituitary are yet unclear. To explore the potential mRNAs and lncRNAs that regulate the expression of the genes involved in sheep prolificacy, we used stranded specific RNA-seq to profile the pituitary transcriptome (lncRNA and mRNA) in high prolificacy (genotype FecB BB, litter size = 3; H) and low prolificacy sheep (genotype FecB B+; litter size = 1; L). Our results showed that 57 differentially expressed (DE) lncRNAs and 298 DE mRNAs were found in the pituitary between the two groups. The qRT-PCR results correlated well with the RNA-seq results. Moreover, functional annotation analysis showed that the target genes of the DE lncRNAs were significantly enriched in pituitary function, hormone-related pathways as well as response to stimulus and some other terms related to reproduction. Furthermore, a co-expression network of lncRNAs and target genes was constructed and reproduction related genes such as SMAD2, NMB and EFNB3 were included. Lastly, the interaction of candidate lncRNA MSTRG.259847.2 and its target gene SMAD2 were validated in vitro of sheep pituitary cells. These differential mRNA and lncRNA expression profiles provide a valuable resource for understanding the molecular mechanisms underlying Hu sheep prolificacy.


Rheumatology ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 430-440
Author(s):  
Xiaohong Fu ◽  
Guojing Song ◽  
Rongrong Ni ◽  
Han Liu ◽  
Zhizhen Xu ◽  
...  

Abstract Objectives Long non-coding RNA H19 (lncRNA-H19) is highly expressed in fibroblast-like synoviocytes (FLS) from patients with RA. The present study aimed to clarify the pathological significance and regulatory mechanisms of lncRNA-H19 in FLS. Methods Mice with CIA were locally injected with LV-shH19. The progression of CIA was explored by measuring arthritic index (AI), paw thickness (PT) and histologic analysis. The growth and cell cycle of human synoviocyte MH7A were assessed by CCK-8 and flow cytometric analysis. The putative binding sites between lncRNA-H19 and miR-124a were predicted online, and the binding was identified by luciferase assay. RT-qPCR, Western blot and luciferase assay were performed to explore the molecular mechanisms between liver X receptor (LXR), lncRNA-H19, miR-124a and its target genes. Results The expression of lncRNA-H19 was closely associated with the proliferation of synoviocytes and knockdown of lncRNA-H19 significantly ameliorated the progression of CIA, reflected by decreased AI, PT and cartilage destruction. Notably, lncRNA-H19 competitively bound to miR-124a, which directly targets CDK2 and MCP-1. It was confirmed that lncRNA-H19 regulates the proliferation of synoviocytes by acting as a sponge of miR-124a to modulate CDK2 and MCP-1 expression. Furthermore, the agonists of LXR inhibited lncRNA-H19-mediated miR-124a-CDK2/MCP-1 signalling pathway in synoviocytes. The ‘lncRNA-H19-miR-124a-CDK2/MCP-1’ axis plays an important role in LXR anti-arthritis. Conclusion Regulation of the miR-124a-CDK2/MCP-1 pathway by lncRNA-H19 plays a crucial role in the proliferation of FLS. Targeting this axis has therapeutic potential in the treatment of RA and may represent a novel strategy for RA treatment.


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