scholarly journals Whole-transcriptome RNA sequencing reveals the global molecular responses and ceRNA regulatory network of mRNAs, lncRNAs, miRNAs and circRNAs in response to Cu toxicity in Ziyang xiangcheng (Citrus junos Sieb. ex Tanaka)

2019 ◽  
Author(s):  
xing-zheng fu ◽  
Xiao-Yong Zhang ◽  
Jie-Ya Qiu ◽  
Xue Zhou ◽  
Meng Yuan ◽  
...  

Abstract Background Copper (Cu) toxicity has become a potential threat for citrus production, but little is known about related mechanisms. This study aims to uncover the global landscape of mRNAs, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) in response to Cu toxicity so as to construct a regulatory network of competing endogenous RNAs (ceRNAs) and to provide valuable knowledge pertinent to Cu response in citrus. Results Tolerance of four commonly used rootstocks to Cu toxicity was evaluated, and ‘Ziyang Xiangcheng’ (Citrus junos ) was found to be the most tolerant genotype. Then the roots and leaves sampled from ‘Ziyang Xiangcheng’ with or without Cu treatment were used for whole-transcriptome sequencing. In total, 5734 and 222 mRNAs, 164 and 5 lncRNAs, 45 and 17 circRNAs, and 147 and 130 miRNAs were identified to be differentially expressed (DE) in Cu-treated roots and leaves, respectively, in comparison with the control. Gene ontology enrichment analysis showed that most of the DEmRNAs and targets of DElncRNAs and DEmiRNAs were annotated to the categories of ‘oxidation-reduction’, ‘phosphorylation’, ‘membrane’, and ‘ion binding’. The ceRNA network was then constructed with the predicted pairs of DEmRNAs-DEmiRNAs and DElncRNAs-DEmiRNAs, which further revealed regulatory roles of these DERNAs in Cu toxicity. Conclusions A large number of mRNAs, lncRNAs, circRNAs, and miRNAs in ‘Ziyang Xiangcheng’ were altered in response to Cu toxicity, which may play crucial roles in mitigation of Cu toxicity through the ceRNA regulatory network in this Cu-tolerant rootstock.

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xing-Zheng Fu ◽  
Xiao-Yong Zhang ◽  
Jie-Ya Qiu ◽  
Xue Zhou ◽  
Meng Yuan ◽  
...  

Abstract Background Copper (Cu) toxicity has become a potential threat for citrus production, but little is known about related mechanisms. This study aims to uncover the global landscape of mRNAs, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) in response to Cu toxicity so as to construct a regulatory network of competing endogenous RNAs (ceRNAs) and to provide valuable knowledge pertinent to Cu response in citrus. Results Tolerance of four commonly used rootstocks to Cu toxicity was evaluated, and ‘Ziyang Xiangcheng’ (Citrus junos) was found to be the most tolerant genotype. Then the roots and leaves sampled from ‘Ziyang Xiangcheng’ with or without Cu treatment were used for whole-transcriptome sequencing. In total, 5734 and 222 mRNAs, 164 and 5 lncRNAs, 45 and 17 circRNAs, and 147 and 130 miRNAs were identified to be differentially expressed (DE) in Cu-treated roots and leaves, respectively, in comparison with the control. Gene ontology enrichment analysis showed that most of the DEmRNAs and targets of DElncRNAs and DEmiRNAs were annotated to the categories of ‘oxidation-reduction’, ‘phosphorylation’, ‘membrane’, and ‘ion binding’. The ceRNA network was then constructed with the predicted pairs of DEmRNAs-DEmiRNAs and DElncRNAs-DEmiRNAs, which further revealed regulatory roles of these DERNAs in Cu toxicity. Conclusions A large number of mRNAs, lncRNAs, circRNAs, and miRNAs in ‘Ziyang Xiangcheng’ were altered in response to Cu toxicity, which may play crucial roles in mitigation of Cu toxicity through the ceRNA regulatory network in this Cu-tolerant rootstock.


2019 ◽  
Author(s):  
Xing-zheng Fu ◽  
Xiao-Yong Zhang ◽  
Jie-Ya Qiu ◽  
Xue Zhou ◽  
Meng Yuan ◽  
...  

Abstract Background Copper (Cu) toxicity has become a potential threat for citrus production, but little is known about related mechanisms. This study aims to uncover the global molecular response of mRNAs, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) to Cu toxicity and to construct their competing endogenous RNAs (ceRNAs) network in citrus.Results In this study, tolerance of four commonly used rootstocks to Cu toxicity was first evaluated, and ‘Ziyang Xiangcheng’ (Citrus junos ) was proved to be tolerant rootstock. Then the Cu-treated and -untreated root (CuR, CKR) and leaf (CuL, CKL) of ‘Ziyang Xiangcheng’ was selected to perform whole-genome transcriptome sequencing. In total, 5734 and 222 mRNAs, 164 and 5 lncRNAs, 45 and 17 circRNAs, and 147 and 130 miRNAs were identified to be differentially expressed (DE) in CuR/CKR and CuL/CKL, respectively. Gene ontology enrichment analysis of these DEmRNAs and targets of DElncRNAs and DEmiRNAs showed that most were annotated to oxidation-reduction, phosphorylation, membrane, and ion binding. The ceRNA network was constructed with the predicted DEmRNAs-DEmiRNAs and DElncRNAs-DEmiRNAs pairs, which further revealed regulatory roles of these DERNAs in Cu toxicity.Conclusions A large number of mRNAs, lncRNAs, circRNAs, and miRNAs were altered in response to Cu toxicity in citrus, and they may play crucial roles in mitigation of Cu toxicity through the ceRNA regulatory network.


Animals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3536
Author(s):  
Lu Xu ◽  
Chengli Liu ◽  
Risu Na ◽  
Weiyi Zhang ◽  
Yongmeng He ◽  
...  

The follicle development (FD) is an important factor determining litter size in animals. Recent studies have found that noncoding RNAs (ncRNAs) play an important role in FD. In particular, the role of the regulatory mechanism of competing endogenous RNAs (ceRNAs) that drive FD has attracted increasing attention. Therefore, this study explored the genetic basis of goat FD by obtaining the complete follicular transcriptome of Dazu black goats at different developmental stages. Results revealed that 128 messenger RNAs (mRNAs), 4 long noncoding RNAs (lncRNAs), 49 microRNAs (miRNAs), and 290 circular RNAs (circRNAs) were significantly differentially expressed (DE) between large and small follicles. Moreover, DEmRNAs were enriched in many signaling pathways related to FD, as well as GO terms related to molecular binding and enzyme activity. Based on the analysis of the ceRNA network (CRN), 34 nodes (1 DElncRNAs, 10 DEcircRNAs, 14 DEmiRNAs, and 9 DEmRNAs) and 35 interactions (17 DEcircRNAs–DEmRNAs, 2 DElncRNAs–DEmiRNAs, and 16 DEmRNA–DEmiRNAs) implied that the CRN could be involved in the FD of goats. In conclusion, we described gene regulation by DERNAs and lncRNA/circRNA–miRNA–mRNA CRNs in the FD of goats. This study provided insights into the genetic basis of FD in precise transcriptional regulation.


2019 ◽  
Vol 158 (3) ◽  
pp. 133-144
Author(s):  
Sheng Li ◽  
Chengzhen Chen ◽  
Menglong Chai ◽  
Jiawei Wang ◽  
Bao Yuan ◽  
...  

Bone morphogenetic protein 2 (BMP2) can mediate the signaling of R-Smads and regulate different biological functions, including adipocyte differentiation. Long noncoding RNAs (lncRNAs) can be involved in many important biological processes, including fat metabolism, as miRNA sponges. This study aimed to investigate the molecular mechanism of fat deposition and to provide useful information for the prevention and treatment of lipid-related diseases. lncRNA sequencing was performed to compare and analyze, for the first time, the expression of lncRNAs in BMP2-induced and non-BMP2-induced preadipocytes from Junmu1 pigs. In addition, functional annotation and enrichment analysis of differentially expressed lncRNA target genes were carried out. lncRNAs and mRNAs were compared and analyzed. lncRNAs were identified that may regulate adipogenesis and lipid metabolism. The results give a theoretical basis for further studies on fat deposition mechanisms and provide potential therapeutic targets for metabolic diseases.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Junzhuo Si ◽  
Xia Tang ◽  
Lei Xu ◽  
Huichao Fu ◽  
Huayi Li ◽  
...  

Abstract Background With the advancement of sequencing technologies, a plethora of noncoding RNA (ncRNA) species have been widely discovered, including microRNAs (miRNAs), circular RNAs (circRNAs), and long ncRNAs (lncRNAs). However, the mechanism of these non-coding RNAs in diseases caused by enterovirus d68 (EV-D68) remains unclear. The goal of this research was to identify significantly altered circRNAs, lncRNAs, miRNAs, and mRNAs pathways in RD cells infected with EV-D68, analyze their target relationships, demonstrate the competing endogenous RNA (ceRNA) regulatory network, and evaluate their biological functions. Methods The total RNAs were sequenced by high-throughput sequencing technology, and differentially expressed genes between control and infection groups were screened using bioinformatics method. We discovered the targeting relationship between three ncRNAs and mRNA using bioinformatics methods, and then built a ceRNA regulatory network centered on miRNA. The biological functions of differentially expressed mRNAs (DEmRNAs) were discovered through GO and KEGG enrichment analysis. Create a protein interaction network (PPI) to seek for hub mRNAs and learn more about protein–protein interactions. The relative expression was verified using RT-qPCR. The effects of Fos and ARRDC3 on virus replication were confirmed using RT-qPCR, virus titer (TCID50/ml), Western blotting. Results 375 lncRNAs (154 upregulated and 221 downregulated), 33 circRNAs (32 upregulated and 1 downregulated), 96 miRNAs (49 upregulated and 47 downregulated), and 239 mRNAs (135 upregulated and 104 downregulated) were identified as differently in infected group compare to no-infected group. A single lncRNA or circRNA can be connected with numerous miRNAs, which subsequently coregulate additional mRNAs, according to the ceRNA regulatory network. The majority of DEmRNAs were shown to be connected to DNA binding, transcription regulation by RNA polymerase II, transcription factor, MAPK signaling pathways, Hippo signal pathway, and apoptosis pathway, according to GO and KEGG pathway enrichment analysis. The hub mRNAs with EGR1, Fos and Jun as the core were screened through PPI interaction network. We preliminarily demonstrated that the Fos and ARRDC3 genes can suppress EV-D68 viral replication in order to further verify the results of full transcriptome sequencing. Conclusion The results of whole transcriptome analysis after EV-D68 infection of RD cells were first reported in this study, and for the first time, a ceRNA regulation network containing miRNA at its center was established for the first time. The Fos and ARRDC3 genes were found to hinder viral in RD cells. This study establishes a novel insight host response during EV-D68 infection and further investigated potential drug targets.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11420
Author(s):  
Haijin Zhang ◽  
Xue Song ◽  
Zongyan Teng ◽  
Sujun Cheng ◽  
Weigang Yu ◽  
...  

Background Osteoporosis (OP) is a systemic disease with bone loss and microstructural deterioration. Numerous noncoding RNAs (ncRNAs) have been proved to participate in various diseases, especially circular RNAs (circRNAs). However, the expression profile and mechanisms underlying circRNAs in male osteoporosis have not yet been explored. Methods The whole transcriptome expression profile and differences in mRNAs, circRNAs, and microRNAs (miRNAs) were investigated in peripheral blood samples of patients with osteoporosis and healthy controls consisting of males ≥ 60-years-old. Results A total of 398 circRNAs, 51 miRNAs, and 642 mRNAs were significantly and differentially expressed in osteoporosis compared to healthy controls. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the host genes of significantly differentially expressed circRNAs were mainly enriched in the regulation of cell cycle process: biological process (BP), organelle part cellular components (CC), protein binding molecular function (MF), Toll-like receptor signaling pathway, tumor necrosis factor (TNF) signaling pathway, and thyroid hormone signaling pathway. circRNA-miRNA-mRNA regulatory network was constructed using the differentially expressed RNAs. Moreover, key circRNAs (hsa_circ_0042409) in osteoporosis were discovered and validated by qPCR. Conclusions The key cicrRNAs plays a major role in the pathogenesis of osteoporosis and could be used as potential biomarkers or targets in the diagnosis and treatment of osteoporosis.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11216
Author(s):  
Jianlei Sun ◽  
Yumei Dong ◽  
Chongqi Wang ◽  
Shouhua Xiao ◽  
Zigao Jiao ◽  
...  

Circular RNAs (circRNAs) are a class of newly discovered non-coding RNAs that are typically derived from a genome’s exonic, intronic, and intergenic regions. Recent studies of circRNAs in animals and plants have shown that circRNAs are vital in response to various abiotic and biotic stresses. Powdery mildew disease (PM) is a serious fungal disease threatening the melon industry. We performed whole transcriptome sequencing using the leaves of a PM-resistant (M1) and a PM-susceptible (B29) melon to identify circRNAs and determine their molecular functions. A total of 303 circRNAs were identified and >50% circRNAs were derived from exonic regions. Expression levels were significantly altered in 17 and 23 circRNAs after PM infections in B29 and M1, respectively. Melon circRNAs may participate in the response to biotic stimuli, oxidation reduction, metabolic processes, and the regulation of gene expression based on the functional annotation of circRNA parental genes. Furthermore, 27 circRNAs were predicted to be potential targets or ‘sponges’ for 18 microRNAs (miRNAs). Our results are the first to identify and characterize circRNA functions in melon and may contribute to a better understanding of the role and regulatory mechanisms of circRNAs in resisting PM.


2021 ◽  
Author(s):  
Xiuchun Li ◽  
Haijian Cai ◽  
Chi Zhang ◽  
Yaxin Zhang ◽  
Xinghong Wang ◽  
...  

Abstract Noncoding RNAs have been shown to play important roles in hypoxic pulmonary hypertension (HPH). Our preliminary data showed that HPH is attenuated by fibroblast growth factor 21 (FGF21) administration. Therefore, we further investigated the whole transcriptome RNA expression patterns and interactions in a mice HPH model treated with FGF21. By whole-transcriptome sequencing, differentially expressed mRNA, miRNA, lncRNA, and circRNA were successfully identified in normoxia (Nx) vs. hypoxia (Hx) and Hx vs. hypoxia + FGF21 (Hx + F21). Through intersection and predictive analysis, differentially co-expressed mRNA, miRNA, lncRNA, and circRNA were selected, followed by functional enrichment analysis. MAPK signaling pathway and epigenetic modification were enriched and may play fundamental roles in the therapeutic effects of FGF21. A ceRNA regulatory network was constructed with miR-7a-5p, miR-449c-5p, miR-676-3p and miR-674-3p as the core. Then the quantitative real time-PCR validation results were consistent with the results of whole-transcriptome sequencing. This study may provide potential biomarkers, pathway and ceRNA regulatory network in HPH treated with FGF21.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lianghai Wang ◽  
Lisha Zhou ◽  
Jun Hou ◽  
Jin Meng ◽  
Ke Lin ◽  
...  

Abstract Background The regulatory roles of circular RNAs (circRNAs) in tumorigenesis have attracted increasing attention. However, novel circRNAs with the potential to be used as serum/plasma biomarkers and their regulatory mechanism in the pathogenesis of hepatocellular carcinoma (HCC) remain explored. Methods CircRNA expression profiles of tumor tissues and plasma samples from HCC patients were compiled and jointly analyzed. CircRNA–miRNA–mRNA interactions were predicted by bioinformatics tools. The expression of interacting miRNAs and mRNA was verified in independent datasets. Survival analysis and pathway enrichment analysis were conducted on hub genes. Results We identified three significantly up-regulated circRNAs (hsa_circ_0009910, hsa_circ_0049783, and hsa_circ_0089172) both in HCC tissues and plasma samples. Two of them were validated to be indeed circular and could be excreted from hepatoma cells. We further revealed four miRNAs (hsa-miR-455-5p, hsa-miR-615-3p, hsa-miR-18a-3p, hsa-miR-4524a-3p) that targeting circRNAs and expressed in human HCC samples, and 95 mRNAs targeted by miRNAs and significantly up-regulated in two HCC cohorts. A protein-protein interaction network revealed 19 hub genes, 12 of them (MCM6, CCNB1, CDC20, NDC80, ZWINT, ASPM, CENPU, MCM3, MCM5, ECT2, CDC7, and DLGAP5) were associated with reduced survival in two HCC cohorts. KEGG, Reactome, and Wikipathway enrichment analysis indicated that the hub genes mainly functioned in DNA replication and cell cycle. Conclusions Our study uncovers three novel deregulated circRNAs in tumor and plasma from HCC patients and provides an insight into the pathogenesis from the circRNA–miRNA–mRNA regulatory network.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yonghui Fu ◽  
Wenfeng He ◽  
Chaoxiong Zhou ◽  
Xia Fu ◽  
Qigen Wan ◽  
...  

Bipolar disorder (BD) is a severe mood disorder disease in China, and its underlying pathogenesis remains unknown. Circular RNAs (circRNAs) have been reported to play a key role in mental disorders and can be used as competitive endogenous RNAs (ceRNAs). However, little is known about the correlation of circRNAs with BD. In this study, Deep RNA sequencing was used to identify differentially expressed circRNAs (DE-circRNAs) and differentially expressed mRNAs (DE-mRNAs) between BD patients and a control group. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to validate the differentially expressed RNAs (DE-RNAs). In all 9,593 circRNAs and 20,030 mRNAs were found in the two groups of specimens, among which 50 DE-circRNAs and 244 DE-mRNAs were significantly upregulated, and 44 DE-circRNAs and 294 DE-mRNAs were significantly downregulated. Based on the regulatory mechanism of ceRNAs, circRNAs can directly bind microRNAs (miRNAs) to affect mRNA expression, and the expression trends of circRNAs and mRNAs are consistent. According to this mechanism, we constructed two ceRNA networks by using the RNA sequencing data. The function of these DE-circRNAs was further elucidated by enrichment analysis. In summary, the present study showed that the circRNA expression profile of BD patients is altered, and a ceRNA regulatory network was constructed, which provided a hypothesis about the pathogenesis of BD.


Sign in / Sign up

Export Citation Format

Share Document