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Effect of simulated microgravity and ionizing radiation on expression profiles of mirna, lncrna, and mrna in human lymphoblastoid cells

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LIFE SCIENCES IN SPACE RESEARCH 2020年 24卷 1-8页

作者： Fu Hanjiang Su Fei Zhu Jie Zheng Xiaofei Ge Changhui Beijing Inst Radiat Med Dept Expt Hematol & Biochem 27 Taiping Rd Beijing 100850 Peoples R China

In space, multiple unique environmental factors, particularly microgravity and space radiation, pose a constant threat to astronaut health. Micrornas (mirnas) and long noncoding rnas (lncrnas) are functional rnas that play critical roles in regulating multiple cellular processes. To gain insight into the role of non-coding rnas in response to radiation and microgravity, we analyzed rna expression profiles in human lymphoblastoid TK6 cells incubated for 24 h under static or rotating conditions to stimulate microgravity in space, after 2-Gy gamma-ray irradiation. The expression of 14 lncrnas and 17 mrnas (differentially-expressed genes, DEGs) was found to be significantly downregulated under simulated microgravity conditions. In contrast, irradiation upregulated 55 lncrnas and 56 DEGs, whereas only one lncrna, but no DEGs, was downregulated. Furthermore, two mirnas, 70 lncrnas, and 87 DEGs showed significantly altered expression in response to simulated microgravity after irradiation, and these changes were independently induced by irradiation and simulated microgravity. GO enrichment and KEGG pathway analyses indicated that the associated target genes showed similar patterns to the noncoding rnas and were suggested to be involved in the immune/inflammatory response including LPS/TLR, TNF, and NF-kappa B signaling pathways. However, synergistic effects on rna expression and cellular responses were also observed with a combination of simulated microgravity and irradiation based on microarray and RT-PCR analysis. Together, our results indicate that simulated microgravity and irradiation additively alter expression patterns but synergistically modulate the expression levels of rnas and their target genes in human lymphoblastoid cells.

关键词： Human lymphoblastoid Irradiation long-noncoding rna microrna Simulated microgravity

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SENCR stabilizes vascular endothelial cell adherens junctions through interaction with CKAP4

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2019年第2期116卷 546-555页

作者： Lyu, Qing Xu, Suowen Lyu, Yuyan Choi, Mihyun Christie, Christine K. Slivano, Orazio J. Rahman, Arshad Jin, Zheng-Gen long, Xiaochun Xu, Yawei Miano, Joseph M. Univ Rochester Sch Med & Dent Aab Cardiovasc Res Inst Rochester NY 14642 USA Tongji Univ Sch Med Shanghai Peoples Hosp 2 Dept Cardiol Shanghai 200072 Peoples R China Albany Med Coll Dept Mol & Cellular Physiol Albany NY 12208 USA Univ Rochester Sch Med & Dent Dept Pediat Rochester NY 14642 USA

SENCR is a human-specific, vascular cell-enriched long-noncoding rna (lncrna) that regulates vascular smooth muscle cell and endothelial cell (EC) phenotypes. The underlying mechanisms of action of SENCR in these and other cell types is unknown. Here, levels of SENCR rna are shown to be elevated in several differentiated human EC lineages subjected to laminar shear stress. Increases in SENCR rna are also observed in the laminar shear stress region of the adult aorta of humanized SENCR-expressing mice, but not in disturbed shear stress regions. SENCR loss-of-function studies disclose perturbations in EC membrane integrity resulting in increased EC permeability. Biotiny-lated rna pull-down and mass spectrometry establish an abundant SENCR-binding protein, cytoskeletal-associated protein 4 (CKAP4);this ribonucleoprotein complex was further confirmed in an rna immuno-precipitation experiment using an antibody to CKAP4. Structure-function studies demonstrate a noncanonical rna-binding domain in CKAP4 that binds SENCR. Upon SENCR knockdown, increasing levels of CKAP4 protein are detected in the EC surface fraction. Furthermore, an interaction between CKAP4 and CDH5 is enhanced in SENCR-depleted EC. This heightened association appears to destabilize the CDH5/CTNND1 complex and augment CDH5 internalization, resulting in impaired adherens junctions. These findings support SENCR as a flow-responsive lncrna that promotes EC adherens junction integrity through physical association with CKAP4, thereby stabilizing cell membrane-bound CDH5.

关键词： long-noncoding rna endothelial cell shear stress adherens junction

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PMS1T, producing phased small-interfering rnas, regulates photoperiod-sensitive male sterility in rice

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2016年第52期113卷 15144-15149页

作者： Fan, Yourong Yang, Jiangyi Mathioni, Sandra M. Yu, Jinsheng Shen, Jianqiang Yang, Xuefei Wang, Lei Zhang, Qinghua Cai, Zhaoxia Xu, Caiguo Li, Xianghua Xiao, Jinghua Meyers, Blake C. Zhang, Qifa Huazhong Agr Univ Natl Ctr Plant Gene Res Wuhan Natl Key Lab Crop Genet Improvement Wuhan 430070 Peoples R China Univ Delaware Delaware Biotechnol Inst Dept Plant & Soil Sci Newark DE 19711 USA Guangxi Univ Coll Life Sci & Technol Nanning 530004 Peoples R China Donald Danforth Plant Sci Ctr St Louis MO 63132 USA Zhejiang A&F Univ Sch Agr & Food Sci Key Lab Qual Improvement Agr Prod Zhejiang Prov Linan 311300 Peoples R China

Phased small-interfering rnas (phasirnas) are a special class of small rnas, which are generated in 21- or 24-nt intervals from transcripts of precursor rnas. Although phasirnas have been found in a range of organisms, their biological functions in plants have yet to be uncovered. Here we show that phasirnas generated by the photopheriod-sensetive genic male sterility 1 (Pms1) locus were associated with photoperiod-sensitive male sterility (PSMS) in rice, a germplasm that started the two-line hybrid rice breeding. The Pms1 locus encodes a long-noncoding rna PMS1T that was preferentially expressed in young panicles. PMS1T was targeted by miR2118 to produce 21-nt phasirnas that preferentially accumulated in the PSMS line under long-day conditions. A single nucleotide polymorphism in PMS1T nearby the miR2118 recognition site was critical for fertility change, likely leading to differential accumulation of the phasirnas. This result suggested possible roles of phasirnas in reproductive development of rice, demonstrating the potential importance of this rna class as regulators in biological processes.

关键词： photoperiod-sensitive male sterility long-noncoding rna phasirna

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Hypoxia-inducible lncrna MIR210HG promotes HIF1a expression by inhibiting miR-93-5p in renal tubular cells

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FEBS JOUrnaL 2023年第16期290卷 4040-4056页

作者： Saigusa, Hanako Mimura, Imari Kurata, Yu Tanaka, Tetsuhiro Nangaku, Masaomi Univ Tokyo Div Nephrol & Endocrinol Grad Sch Med 7-3-1 HongoBunkyo Ku Tokyo 1138655 Japan Tohoku Univ Dept Nephrol Rheumatol & Endocrinol Grad Sch Med Sendai Japan

Chronic hypoxia in the renal tubular interstitium has been reported to contribute to the progression of chronic kidney disease. Recently, long-noncoding rnas have been shown to be involved in various pathological conditions, including hypoxia, one of which is the MIR210 host gene (MIR210HG). To elucidate the function of MIR210HG in renal hypoxia, we exposed primary cultured renal proximal tubular epithelial cells to hypoxia and examined the temporal profile of MIR210HG expression and the role of MIR210HG interaction with hypoxia-inducible factor1a (HIF1a, encoded by HIF1A). MIR210HG expression was induced by hypoxia. HIF1A silencing and cobalt chloride exposure showed that MIR210HG expression in hypoxia is HIF1a-dependent. MIR210HG silencing significantly reduced both the mrna and protein levels of HIF1a, pointing to positive feedback regulation. To further investigate the details of this regulation, we turned to the in-silico mirna targets of MIR210HG. We found that miR-93-5p levels increased when MIR210HG was knocked down. We then showed that miR-93-5p reduced the expression of HIF1A mrna and MIR210HG. Furthermore, a dual luciferase assay confirmed that miR-93-5p binds to MIR210HG and HIF1A 3' UTR, inhibiting their expression. In conclusion, the long-noncoding rna MIR210HG is induced shortly after hypoxia, and it promotes HIF1a expression by competing for miR-93-5p and inhibiting it. MIR210HG plays a crucial role in the biological response to hypoxia in renal tubular epithelial cells.

关键词： HIF1 hypoxia long-noncoding rna MIR210HG miR-93-5p

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Epigenetic Components of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Uncover Potential Transposable Element Activation

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CLINICAL THERAPEUTICS 2019年第4期41卷 675-698页

作者： Almenar-Perez, Eloy Ovejero, Tamara Sanchez-Fito, Teresa Espejo, Jose A. Nathanson, Lubov Oltra, Elisa Univ Catolica Valencia San Vicente Martir Escuela Doctorado Valencia Spain Univ Catolica Valencia San Vicente Martir Sch Med Valencia 46001 Spain Univ Catolica Valencia San Vicente Martir Sch Expt Sci Valencia Spain Nova Southeastern Univ Kiran C Patel Coll Osteopath Med Ft Lauderdale FL 33314 USA Nova Southeastern Univ Inst Neuro Immune Med Ft Lauderdale FL 33314 USA Ctr Invest Principe Felipe Unidad Mixta CIPF UCV Valencia Spain

Purpose: Studies to determine epigenetic changes associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remain scarce;however, current evidence clearly shows that methylation patterns of genomic DNA and noncoding rna profiles of immune cells differ between patients and healthy subjects, suggesting an active role of these epigenetic mechanisms in the disease. The present study compares and contrasts the available ME/CFS epigenetic data in an effort to evidence overlapping pathways capable of explaining at least some of the dysfunctional immune parameters linked to this disease. Methods: A systematic search of the literature evaluating the ME/CFS epigenome landscape was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Differential DNA methylation and noncoding rna differential expression patterns associated with ME/CFS were used to screen for the presence of transposable elements using the Dfam browser, a search program nurtured with the Repbase repetitive sequence database and the RepeatMasker annotation tool. Findings: Unexpectedly, particular associations of transposable elements and ME/CFS epigenetic hallmarks were uncovered. A model for the disease emerged involving transcriptional induction of endogenous dormant transposons and structured cellular rna interactions, triggering the activation of the innate immune system without a concomitant active infection. (C) 2019 Elsevier Inc. All rights reserved.

关键词： epigenetic long-noncoding rna microrna myalgic encephalomyelitis/chronic fatigue syndrome retrotransposon transposable elements

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Deletion of the sclerotome-enriched lncrna PEAT augments ribosomal protein expression

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2017年第1期114卷 101-106页

作者： Stafford, David A. Dichmann, Darwin S. Chang, Jessica K. Harland, Richard M. Univ Calif Berkeley Dept Mol & Cell Biol 229 Stanley Hall Berkeley CA 94720 USA Stanford Univ Dept Genet Stanford CA 94305 USA

To define a complete catalog of the genes that are activated during mouse sclerotome formation, we sequenced rna from embryonic mouse tissue directed to form sclerotome in culture. In addition to well-known early markers of sclerotome, such as Pax1, Pax9, and the Bapx2/Nkx3-2 homolog Nkx3-1, the long-noncoding rna PEAT (Pax1 enhancer antisense transcript) was induced in sclerotome-directed samples. Strikingly, PEAT is located just upstream of the Pax1 gene. Using CRISPR/Cas9, we generated a mouse line bearing a complete deletion of the PEAT-transcribed unit. rna-seq on PEAT mutant embryos showed that loss of PEAT modestly increases bone morphogenetic protein target gene expression and also elevates the expression of a large subset of ribosomal protein mrnas.

关键词： sclerotome CRISPR/Cas9 long-noncoding rna ribosomal proteins BMP pathway

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noncoding rnas and Stroke

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NEUROSCIENTIST 2019年第1期25卷 22-26页

作者： Zhang, Xuejing Hamblin, Milton H. Yin, Ke-Jie Univ Pittsburgh Pittsburgh Inst Brain Disorders & Recovery Dept Neurol Sch Med S514 BST200 Lothrop St Pittsburgh PA 15213 USA Tulane Univ Sch Med Dept Pharmacol New Orleans LA 70112 USA

Over many years, extensive efforts have focused on the development and improvement of diagnostic and therapeutic strategies to reduce stroke-associated neurovascular damage, such as blood-brain barrier dysfunction, brain edema, parenchymal inflammation, and neural cell death. However, the only clinically applied pharmacological therapy to date for the treatment of acute ischemic stroke is thrombolysis. Because of the short therapeutic window of current thrombolytic therapy and the activation of various pathophysiological signaling cascades triggered after ischemic stroke, the development of new therapies is urgently required. noncoding rnas (ncrnas) are defined as untranslated regulatory rna molecules. Although ncrnas with biological roles have been known for almost 60 years, they have within the past decade emerged as key mediators of posttranscriptional gene expression/function in pathological aspects of ischemic stroke. With properties of relative stability, specificity, and reproducibility, ncrnas are considered to be promising as biomarkers and better candidates than proteins and genes for early recognition of the onset of disease. In this update, we summarized the current knowledge for three groups of ncrnas in stroke, focusing on the role of long noncoding rnas and circular rnas as biomarkers for stroke and as targets for regulating large sets of genes in related pathways after ischemic stroke.

关键词： noncoding rna stroke microrna long-noncoding rna circular rna

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long non-coding rna HIF1A-AS2 promotes carcinogenesis by enhancing Gli1-mediated HIF1α expression in clear cell renal cell carcinoma

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PATHOLOGY RESEARCH AND PRACTICE 2024年 253卷 154984页

作者： Li, Xiangyun Wu, Yuankai Xiao, Zhini Liu, Yang Wang, Chaofu Zhou, Luting Yang, Xiaoqun Shanghai Jiao Tong Univ Sch Med Ruijin Hosp Dept Pathol Shanghai Peoples R China

Background: The most common urologic tumor in humans with the highest incidence rate is clear cell renal cell carcinoma (ccRCC). long non-coding rnas (lncrnas) act as regulatory factors in several tumors. Here, we studied ccRCC regulated by hypoxia-inducible factor 1 alpha (HIF1 alpha)-antisense rna 2 (AS2) or HIF1A-AS2. Methods: We performed wound-healing, transwell, and CCK-8 assays by decreasing or increasing the HIF1A-AS2 expression in RCC cell lines. Western blotting and qRT-PCR were used to identify the expression of downstream genes of the HIF1A-AS2 pathway. Gli1 and HIF1A-AS2 relationship was assessed using RIP and rna pull-down assays. Lastly, transcriptome sequencing was performed on kidney cancer cells that had been knocked down to find possible regulatory mechanisms. Results: Our results suggest that high expression of HIF1A-AS2 may promote RCC cell proliferation and Gli1 expression as a downstream factor. Furthermore, they have physical binding sites and together regulate HIF1 alpha to encourage the development of ccRCC. HIF1A-AS2 lncrna may offer a new molecular target for ccRCC treatment. Conclusion: lncrna HIF1A-AS2 affects ccRCC development by regulating HIF1a expression through Gli1.

关键词： long-noncoding rna HIF1A-AS2 Clear cell renal cell carcinoma Gli1

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Identification of male infertility-related long non-coding rnas and their functions based on a competing endogenous rna network

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JOUrnaL OF INTErnaTIONAL MEDICAL RESEARCH 2020年第10期48卷 300060520961277-300060520961277页

作者： Zhou, Zuo Wang, Bing Hosp Zibo City Dept Obstet Maternal & Child Hlth Zibo Shandong Peoples R China Hosp Zibo City Ctr Reprod Med Maternal & Child Hlth 11 Xingyuan East Rd Zibo Shandong Peoples R China

Objective To identify male infertility-related long non-coding (lnc)rnas and an lncrna-related competing endogenous (ce)rna network. Methods Expression data including 13 normospermic and eight teratozoospermic samples from postmortem donors were downloaded from the GEO database (GSE6872). The limma R package was used to discriminate dysregulated lncrna and micro (m)rna profiles. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of differentially expressed (DE) mrnas were performed using the clusterProfiler R package. The cerna network of dysregulated genes was visualized by Cytoscape. Results A total of 101 DE lncrnas and 1722 mrnas were identified as male infertility-specific rnas with thresholds of |log(2)FoldChange| >2.0 and adjustedP-value <0.05. GO and KEGG pathways were analyzed for DE mrnas. Gene set enrichment analysis revealed that DE genes were enriched in embryonic skeletal system development and cytokine-cytokine receptor interactions. A cerna network was constructed with 26 key lncrnas, 33 micrornas, and 133 mrnas. DE lncrnas in male sterility were mainly associated with transferring phosphorus-containing groups and complexes of histone methyltransferases, methyltransferases, PcG proteins, and serine/threonine protein kinases. Conclusion This provides a novel perspective to study lncrna-related cerna networks in male infertility and assist in identifying new potential biomarkers for diagnostic purposes.

关键词： Male infertility competing endogenous rna long-noncoding rna gene set enrichment analysis differential expression gene ontology Kyoto Encyclopedia of Genes and Genomes

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A mirna and a lncrna

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2019年第4期520卷 701-701页

作者： Su, Bing Shanghai Jiao Tong Univ Sch Med Dept Immunol & Microbiol Shanghai Inst Immunol 280 South Chongqing RdBldg FiveRoom 1101 Shanghai 200025 Peoples R China

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