scholarly journals Transcriptome-wide map of m6A circRNAs identified in a rat model of hypoxia mediated pulmonary hypertension

2020 ◽  
Author(s):  
Hua Su ◽  
Guowen Wang ◽  
Lingfang Wu ◽  
Xiuqing Ma ◽  
Kejing Ying ◽  
...  

Abstract Background: Hypoxia mediated pulmonary hypertension (HPH) is a lethal disease and lacks effective therapy. CircRNAs play significant roles in physiological process. Recently, circRNAs are found to be m 6 A-modified. The abundance of circRNAs was influenced by m 6 A. Furthermore, the significance of m 6 A circRNAs has not been elucidated in HPH yet. Here we aim to investigate the transcriptome-wide map of m 6 A circRNAs in HPH. Results: Differentially expressed m 6 A abundance was detected in lungs of HPH rats. M 6 A abundance in circRNAs was significantly reduced in hypoxia in vitro . M 6 A circRNAs were mainly from protein-coding genes spanned single exons in control and HPH groups. Moreover, m 6 A influenced the circRNA–miRNA–mRNA co-expression network in hypoxia. M 6 A circXpo6 and m 6 A circTmtc3 were firstly identified to be downregulated in HPH. Conclusion: Our study firstly identified the transcriptome-wide map of m 6 A circRNAs in HPH. M 6 A can influence circRNA–miRNA–mRNA network. Furthermore, we firstly identified two HPH-associated m 6 A circRNAs: circXpo6 and circTmtc3. However, the clinical significance of m 6 A circRNAs for HPH should be further validated. Key words: m 6 A circRNAs; hypoxia mediated pulmonary hypertension; m 6 A circXpo6; m 6 A circTmtc3

2020 ◽  
Author(s):  
Hua Su ◽  
Guowen Wang ◽  
Lingfang Wu ◽  
Xiuqing Ma ◽  
Kejing Ying ◽  
...  

Abstract Background: Hypoxia mediated pulmonary hypertension (HPH) is a lethal disease and lacks effective therapy. CircRNAs play significant roles in physiological process. Recently, circRNAs are found to be m 6 A-modified. The abundance of circRNAs was influenced by m 6 A. Furthermore, the significance of m 6 A circRNAs has not been elucidated in HPH yet. Here we aim to investigate the transcriptome-wide map of m 6 A circRNAs in HPH. Results: Differentially expressed m 6 A abundance was detected in lungs of HPH rats. M 6 A abundance in circRNAs was significantly reduced in hypoxia in vitro . M 6 A circRNAs were mainly from protein-coding genes spanned single exons in control and HPH groups. Moreover, m 6 A influenced the circRNA–miRNA–mRNA co-expression network in hypoxia. M 6 A circXpo6 and m 6 A circTmtc3 were firstly identified to be downregulated in HPH. Conclusion: Our study firstly identified the transcriptome-wide map of m 6 A circRNAs in HPH. M 6 A can influence circRNA–miRNA–mRNA network. Furthermore, we firstly identified two HPH-associated m 6 A circRNAs: circXpo6 and circTmtc3. However, the clinical significance of m 6 A circRNAs for HPH should be further validated. Key words: m 6 A circRNAs; hypoxia mediated pulmonary hypertension; m 6 A circXpo6; m 6 A circTmtc3


2019 ◽  
Author(s):  
Hua Su ◽  
Guowen Wang ◽  
Lingfang Wu ◽  
Xiuqing Ma ◽  
Kejing Ying ◽  
...  

Abstract Background: Hypoxic pulmonary hypertension (HPH) is a lethal disease and lacks effective therapy. CircRNAs play significant roles in physiological process. Recently, circRNAs are found to be m6A-modified. The abundance of circRNAs was influenced by m6A. Furthermore, the significance of m6A circRNAs has not been elucidated in HPH yet. Here we aim to investigate the transcriptome-wide map of m6A circRNAs in HPH. Results: Differentially expressed m6A abundance was detected in lungs of HPH rats. M6A abundance in circRNAs was significantly reduced in hypoxia in vitro. M6A circRNAs were mainly from protein-coding genes spanned single exons in control and HPH groups. Moreover, m6A influenced the circRNA–miRNA–mRNA co-expression network in hypoxia. M6A circXpo6 and m6A circTmtc3 were firstly identified to be downregulated in HPH. Conclusion: Our study firstly identified the transcriptome-wide map of m6A circRNAs in HPH. M6A can influence circRNA–miRNA–mRNA network. Furthermore, we firstly identified two HPH-associated m6A circRNAs: circXpo6 and circTmtc3. However, the clinical significance of m6A circRNAs for HPH should be further validated. Key words: m6A circRNAs; hypoxic pulmonary hypertension; m6A circXpo6; m6A circTmtc3


2019 ◽  
Author(s):  
Hua Su ◽  
Guowen Wang ◽  
Lingfang Wu ◽  
Xiuqing Ma ◽  
Kejing Ying ◽  
...  

Abstract Background: Hypoxic pulmonary hypertension (HPH) is a lethal disease and lacks effective therapy. CircRNAs play significant roles in physiological process. Recently, circRNAs are found to be m 6 A-modified. The abundance of circRNAs was influenced by m 6 A. Furthermore, the significance of m 6 A circRNAs has not been elucidated in HPH yet. Here we aim to investigate the transcriptome-wide map of m 6 A circRNAs in HPH. Results: Differentially expressed m 6 A abundance was detected in lungs of HPH rats. M 6 A abundance in circRNAs was significantly reduced in hypoxia in vitro . M6A circRNAs were mainly from protein-coding genes spanned single exons in control and HPH groups. Moreover, m 6 A influenced the circRNA–miRNA–mRNA co-expression network in hypoxia. M 6 A circXpo6 and m 6 A circTmtc3 were firstly identified to be downregulated in HPH. Conclusion: Our study firstly identified the transcriptome-wide map of m 6 A circRNAs in HPH. M 6 A can influence circRNA–miRNA–mRNA network. Furthermore, we firstly identified two HPH-associated m 6 A circRNAs: circXpo6 and circTmtc3. We suggested that m 6 A circRNAs may be used as a potential therapy targets or biomarkers.


BMC Genomics ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Huan Wang ◽  
Ren Biao Chen ◽  
Si Ni Zhang ◽  
Rui Feng Zhang

Abstract Background Long non-coding RNAs (lncRNAs) play a critical role in the pathogenesis of hypoxic pulmonary hypertension (HPH). The role of N7-methylguanosine (m7G) modification in lncRNAs has received increased attentions in recent years. However, the m7G-methylation of lncRNA in HPH has yet to be determined. We have therefore performed a transcriptome-wide analysis of m7G lncRNAs in HPH. Results Differentially-expressed m7Gs were detected in HPH, and m7G lncRNAs were significantly upregulated compared with non-m7G lncRNAs in HPH. Importantly, this was the first time that the upregulated m7G lncXR_591973 and m7G lncXR_592398 were identified in HPH. Conclusion This study provides the first m7G transcriptome-wide analysis of HPH. Importantly, two HPH-associated m7G lncRNAs were identified, although their clinical significance requires further validation.


2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Yinyin Qu ◽  
Hongyi Li ◽  
Chengmei Shi ◽  
Min Qian ◽  
Ning Yang ◽  
...  

Long noncoding RNAs (lncRNAs) play important roles in brain function modulation and neurodegenerative diseases. However, whether lncRNA regulations are involved in the mechanisms of perioperative neurocognitive disorders, especially in anesthesia-related brain dysfunction, remain unknown. Therefore, we explored the expression and regulation pattern profiles of lncRNAs in the hippocampus of aged rats after sevoflurane anesthesia. Three lncRNAs and 772 protein-coding genes were identified by microarray analysis and evidenced by in vitro and in vivo experiments as differentially expressed. Functional annotation and differentially expressed- (DE-) lncRNA-mRNA coexpression networks reveal that DE-lncRNAs are associated with mitochondrial dysfunction and oxidative stress, aging-related metabolism alterations, DNA damage, and apoptosis, as well as neurodegenerative features during sevoflurane anesthesia. These results suggest that lncRNAs play roles in general anesthesia-related brain function modulation during the perioperative context and provide insights into the lncRNA-related modulation mechanisms and targets.


2019 ◽  
Vol 8 (39) ◽  
Author(s):  
Atthaphon Konyanee ◽  
Panjamaporn Yotpanya ◽  
Marutpong Panya ◽  
Chulapan Engchanil ◽  
Namfon Suebwongsa ◽  
...  

We report the genome sequence of Lactobacillus fermentum 47-7, a good in vitro probiotic strain isolated from an infant. Its genome size is 1.83 Mb, it is assembled from 180 contigs, and it consists of 1,636 protein-coding genes, 15 rRNAs, 57 tRNAs, and 4 noncoding RNAs. This genome sequence will be useful for a variety of applications.


2019 ◽  
Author(s):  
Hua Su ◽  
Lin Zhou ◽  
Na Li ◽  
Guowen Wang ◽  
Lingfang Wu ◽  
...  

AbstractHypoxic pulmonary hypertension (HPH) is a lethal disease. CircRNAs and m6A circRNAs have been reported to be associated with cancer progression, but the expression profiling of m6A circRNAs has not been identified in HPH. This study was to investigate the transcriptome-wide map of m6A circRNAs in HPH. In this study, hypoxia-induced PH rat model was established. Total RNA was extracted and purified from lungs of rats, then circRNAs were detected and annotated by RNA-seq analysis. m6A RNA Immunoprecipitation (MeRIP) was performed following rRNA depletion, and RNA-seq library was constructed. CircRNA–miRNA–mRNA co-expression network was also constructed. In vitro, total m6A was measured. m6A circXpo6 and m6A circTmtc3 were detected in pulmonary artery smooth muscle cells (PASMCs) and pulmonary artery endothelial cells (PAECs) exposed to 21% O2 and 1% O2 for 48 h, respectively. m6A abundance in 166 circRNAs was significantly upregulated and m6A abundance in 191 circRNAs was significantly downregulated in lungs of HPH rats. m6A abundance in circRNAs was significantly reduced in hypoxia in vitro. m6A circRNAs were mainly derived from single exons of protein-coding genes. m6A influenced the circRNA–miRNA–mRNA co-expression network in hypoxia. m6A circXpo6 and m6A circTmtc3 were downregulated in hypoxia. In general, our study firstly identified the transcriptome-wide map of m6A circRNAs in HPH. m6A level in circRNAs was decreased in lungs of HPH rats and in PASMCs and PAECs exposed to hypoxia. Downregulated or upregulated m6A level influenced circRNA–miRNA–mRNA co-expression network in HPH. Moreover, we firstly identified two downregulated m6A circRNAs in HPH: circXpo6 and circTmtc3. We suggested that m6A circRNAs may be used as a potential diagnostic marker or therapy target in the future.Author summaryHPH is a disease with great morbidity and mortality. It is often caused by chronic hypoxic lung diseases, such as chronic obstructive pulmonary disease and interstitial lung diseases. It lacks effective therapy methods so far. CircRNAs are a type of non-coding RNAs and can be used as biomarkers because they are differentially enriched in specific cell types or tissues and not easily degraded. m6A is identified as the most universal modification on non-coding RNAs in eukaryotes. CircRNAs can be modified by m6A. m6A circRNAs in HPH is not well understood yet. Here we identify the transcriptome-wide map of m6A circRNAs in HPH. We elucidate that m6A level in circRNAs is decreased in lungs of HPH rats and in PASMCs and PAECs exposed to hypoxia. We find that downregulated or upregulated m6A level influences circRNA– miRNA–mRNA co-expression network in HPH. Moreover, we are the first to identify two downregulated m6A circRNAs in HPH: circXpo6 and circTmtc3. We suggest that m6A circRNAs may be used as a potential diagnostic marker or therapy target in the future.


2020 ◽  
Author(s):  
Xiao Ma ◽  
Shuangshuang Cen ◽  
Luming Wang ◽  
Chao Zhang ◽  
Limin Wu ◽  
...  

Abstract Background: The gonad is the major factor affecting animal reproduction. The regulatory mechanism of the expression of protein-coding genes involved in reproduction still remains to be elucidated. Increasing evidence has shown that ncRNAs play key regulatory roles in gene expression in many life processes. The roles of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in reproduction have been investigated in some species. However, the regulatory patterns of miRNA and lncRNA in the sex biased expression of protein coding genes remains to be elucidated. In this study, we performed an integrated analysis of miRNA, messenger RNA (mRNA), and lncRNA expression profiles to explore their regulatory patterns in the female ovary and male testis of Chinese soft-shelled turtle, Pelodiscus sinensis.Results: We identified 10 446 mature miRNAs, 20 414 mRNAs and 28 500 lncRNAs in the ovaries and testes, and 633 miRNAs, 11 319 mRNAs, and 10 495 lncRNAs showed differential expression. A total of 2 814 target genes were identified for miRNAs. The predicted target genes of these differentially expressed (DE) miRNAs and lncRNAs included abundant genes related to reproductive regulation. Furthermore, we found that 189 DEmiRNAs and 5 408 DElncRNAs showed sex-specific expression. Of these, 3 DEmiRNAs and 917 DElncRNAs were testis-specific, and 186 DEmiRNAs and 4 491 DElncRNAs were ovary-specific. We further constructed complete endogenous lncRNA-miRNA-mRNA networks using bioinformatics, including 103 DEmiRNAs, 636 DEmRNAs, and 1 622 DElncRNAs. The target genes for the differentially expressed miRNAs and lncRNAs included abundant genes involved in gonadal development, including Wt1, Creb3l2, Gata4, Wnt2, Nr5a1, Hsd17, Igf2r, H2afz, Lin52, Trim71, Zar1, and Jazf1.Conclusions: In animals, miRNA and lncRNA as master regulators regulate reproductive processes by controlling the expression of mRNAs. Considering their importance, the identified miRNAs, lncRNAs, and their targets in P. sinensis might be useful for studying the molecular processes involved in sexual reproduction and genome editing to produce higher quality aquaculture animals. A thorough understanding of ncRNA-based cellular regulatory networks will aid in the improvement of P. sinensis reproductive traits for aquaculture.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3260-3260
Author(s):  
Rosana A Silveira ◽  
Angela A Fachel ◽  
Yuri B Moreira ◽  
Marcia T Delamain ◽  
Carmino Antonio De Souza ◽  
...  

Abstract Abstract 3260 Poster Board III-1 Background: CML treatment with tyrosine kinase inhibitors induces high and durable rates of complete cytogenetic response. Despite treatment efficacy, a significant proportion of patients develop resistance to these drugs. We measured gene expression profiles in an attempt to identify gene pathways that may be associated with dasatinib resistance. Patients and Methods: Mononuclear cells were separated from peripheral blood samples from seven CML patients resistant to imatinib, collected prior and after dasatinib treatment. Three patients who achieved partial cytogenetic response (Ph-positive cells: 1% - 35%) within twelve months were considered responders (R), whereas four patients who failed to achieve PCyR within 12 months of treatment were classified as non-responders. RNA samples prepared from peripheral mononuclear cells were hybridized to Agilent Technologies 4×44K Whole Human Genome Microarrays (WHGM) and 4×44K intronic-exonic custom oligoarrays. The latter was developed by Verjovski-Almeida's group (Nakaya et al, Genome Biology 2007, 8:R43) and contains sense and antisense probes that map to intronic regions in the human genome representing totally (TIN) and partially (PIN) intronic non-coding RNAs (ncRNAs), in addition to probes for the corresponding protein-coding genes of the same loci. Raw microarray data were normalized by the Affy package in statistical R language implemented in the Bioconductor platform. Each sample was labeled in replicate with Cy3 or Cy5 and the two were considered technical replicates. Two independent statistical approaches SAM (Significance Analysis of Microarrays) and Golub's discrimination score (SNR, Signal to Noise Ratio, with permutations) were performed to identify differentially expressed transcripts between responder and non-responder patients. For the intronic-exonic platform, the analysis parameters were FDR 10%, SNR>1.5 and p<0.01, and for WHGM platform parameters were FDR 5%, SNR>1.5 and p<0.001. For this latter platform, we also performed a patient leave-one-out analysis. Functions of transcripts differentially expressed were annotated and compared using GO Biological Process categories (www.genetools.microarray.ntu.no/egon). Results: We identified 34 ncRNAs with altered expression (26 over and 8 underexpressed in responders) in pre-treatment samples and 33 ncRNAs (20 over and 13 underexpressed in responders) in post-treatment samples. Functions associated with protein-coding genes from the same genomic loci as those of the intronic differentially expressed ncRNAs were: regulation of transcription (PRMT5, SOD2, SSBP3, BCL7A, MLL), signal transduction (PRKCB1, RASGRP2, NF1, PXN) and apoptosis (BCL2, PCSK6, TNFAIP8, EIF4G2). WHGM platform data analysis showed 63 and 250 protein-coding genes differentially expressed in pre and post-treatment samples, respectively. We observed a higher number of protein-coding genes with altered expression after treatment in the following functions: cell communication, immune response and metabolic process (p<0.02). Conclusions: Overall, these findings indicate that protein-coding genes and intronic ncRNAs may be related to dasatinib resistance and response to treatment. In particular, altered expression of ncRNAs transcribed from the introns of ‘regulation of transcription' genes could be part of an important alternative mechanism of gene expression control during emergence of resistance.Support: FAPESP (2005/60266-8) Disclosures: No relevant conflicts of interest to declare.


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