scholarly journals Identification of a Distinct miRNA Regulatory Network in the Tumor Microenvironment of Transformed Mycosis Fungoides

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5854
Author(s):  
Cosimo Di Raimondo ◽  
Zhen Han ◽  
Chingyu Su ◽  
Xiwei Wu ◽  
Hanjun Qin ◽  
...  

Large cell transformation of mycosis fungoides (LCT-MF) occurs in 20–50% of advanced MF and is generally associated with poor response and dismal prognosis. Although different mechanisms have been proposed to explain the pathogenesis, little is known about the role of microRNAs (miRs) in transcriptional regulation of LCT-MF. Here, we investigated the miR and mRNA expression profile in lesional skin samples of patients with LCT-MF and non-LCT MF using RNA-seq analysis. We found miR-146a and miR-21 to be significantly upregulated, and miR-708 the most significantly downregulated miR in LCT-MF. Integration of miR and mRNA expression profiles revealed the miR-regulated networks in LCT-MF. Ingenuity pathway analysis (IPA) demonstrated the involvement of genes for ICOS-ICOSL, PD1-PDL1, NF-κB, E2F transcription, and molecular mechanisms of cancer signaling pathways. Quantitative real time (qRT)-PCR results of target genes were consistent with the RNA-seq data. We further identified the immunosuppressive tumor microenvironment (TME) in LCT-MF. Moreover, our data indicated that miR-146a, -21 and -708 are associated with the immunosuppressive TME in LCT-MF. Collectively, our results suggest that the key LCT-MF associated miRs and their regulated networks may provide insights into its pathogenesis and identify promising targets for novel therapeutic strategies.

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.


2020 ◽  
Author(s):  
Jiaoyan Tan ◽  
Yan Wu ◽  
Jianping Guo ◽  
Huimin Li ◽  
Lili Zhu ◽  
...  

Abstract Background : The brown planthopper (BPH, Nilaparvata lugens Stål) is a kind of phloem-feeding pest that adversely affects rice yield. Recently, the BPH-resistance gene, BPH6 , was cloned and applied in rice breeding to effectively control BPH. However, the molecular mechanisms underlying BPH6 are poorly understood. Results: Here, an integrated miRNA and mRNA expression profiling analysis was performed on BPH6 -transgenic (BPH6G) and Nipponbare (wild type, WT) plants after BPH infestation, and a total of 217 differentially expressed miRNAs (DEMs) and 7,874 differentially expressed mRNAs (DEGs) were identified. 29 miRNAs, including members of miR160, miR166 and miR169 family were opposite expressed during early or late feeding stages between the two varieties, whilst 9 miRNAs were specifically expressed in BPH6G plants, suggesting involvement of these miRNAs in BPH6 -mediated resistance to BPH. In the transcriptome analysis, 949 DEGs were opposite expressed during early or late feeding stages of the two genotypes, which were enriched in metabolic processes, cellular development, cell wall organization, cellular component movement and hormone transport, and certain primary and secondary metabolite synthesis. 24 genes were further selected as candidates for BPH resistance. Integrated analysis of the DEMs and DEGs showed that 34 miRNAs corresponding to 42 target genes were candidate miRNA-mRNA pairs for BPH resistance, 18 pairs were verified by qRT-PCR, and two pairs were confirmed by in vivo analysis. Conclusions: For the first time, we reported integrated small RNA and transcriptome sequencing to illustrate resistance mechanisms against BPH in rice. Our results provide a valuable resource to ascertain changes in BPH-induced miRNA and mRNA expression profiles and enable to comprehend plant-insect interactions and find a way for efficient insect control.


2019 ◽  
Vol 20 (5) ◽  
pp. 1041 ◽  
Author(s):  
Shuo Gao ◽  
Hao Jiang ◽  
Jie Sun ◽  
Youxiang Diao ◽  
Yi Tang ◽  
...  

The Reticuloendotheliosis virus (REV) primarily causes avian severe immunosuppression, in addition to other symptoms, which include avian dwarfing syndrome and chronic tumors in lymphoid and other tissue. To date, REV’s molecular mechanisms leading to immunosuppression have not been fully elucidated. In the current study, we aimed to elucidate the role of microRNAs (miRNA) in regulating gene expression during REV infections. Therefore, we used a high-dose spleen necrosis virus (SNV) model of REV to inoculate one-day-old specific pathogen-free (SPF) chickens, thereby inducing congenital infections. We analyzed miRNA and mRNA expression profiles using Next Generation Sequencing (NGS) in a total of 19 spleen samples that were collected at 7, 14, and 21 days post infection (dpi). The results showed that 63 differentially expressed miRNAs (DEmiRNAs) (30 known miRNAs and 33 novel miRNAs) and 482 differentially expressed target genes (DETGs) were identified. Integration analysis identified 886 known miRNA–mRNA and 580 novel miRNA–mRNA interaction pairs, which involved miRNAs that were inversely correlated with the above DETGs. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the DETGs were considerably enriched in the immune-relevant pathways category, such as immune system, cell growth and death, signaling molecules and interaction, signal transduction, etc. We further verified selected immune-relevant miRNA and their DETGs while using quantitative RT-PCR (qRT-PCR). Overall, our data revealed valuable immune-related miRNA–mRNA interaction information that occurred during REV infections, thereby broadening our understanding of the REV-induced immunosuppression.


2019 ◽  
Author(s):  
Jiaoyan Tan ◽  
Yan Wu ◽  
Jianping Guo ◽  
Huimin Li ◽  
Lili Zhu ◽  
...  

Abstract Background: The brown planthopper (BPH, Nilaparvata lugens Stål) is a kind of phloem-feeding pest that adversely affects rice yield. Recently, the BPH-resistance gene, BPH6, was cloned and applied in rice breeding to effectively control BPH. However, the molecular mechanisms underlying BPH6 are poorly understood. Results: Here, an integrated miRNA and mRNA expression profiling analysis was performed on BPH6-transgenic (BPH6G) and Nipponbare (wild type, WT) plants after BPH infestation, and a total of 217 differentially expressed miRNAs (DEMs) and 7,874 differentially expressed mRNAs (DEGs) were identified. 29 miRNAs, including members of miR160, miR166 and miR169 family were opposite expressed during early or late feeding stages between the two varieties, whilst 9 miRNAs were specifically expressed in BPH6G plants, suggesting involvement of these miRNAs in BPH6-mediated resistance to BPH. In the transcriptome analysis, 949 DEGs were opposite expressed during early or late feeding stages of the two genotypes, which were enriched in metabolic processes, cellular development, cell wall organization, cellular component movement and hormone transport, and certain primary and secondary metabolite synthesis. 24 genes were further selected as candidates for BPH resistance. Integrated analysis of the DEMs and DEGs showed that 34 miRNAs corresponding to 42 target genes were candidate miRNA-mRNA pairs for BPH resistance, 18 pairs were verified by qRT-PCR, and two pairs were confirmed by in vivo analysis. Conclusions: For the first time, we reported integrated small RNA and transcriptome sequencing to illustrate resistance mechanisms against BPH in rice. Our results provide a valuable resource to ascertain changes in BPH-induced miRNA and mRNA expression profiles and enables the analysis of the comprehensive plant-insect interactions required for efficient insect control.


2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Peng Li Zhou ◽  
Zhengyang Wu ◽  
Wenguang Zhang ◽  
Miao Xu ◽  
Jianzhuang Ren ◽  
...  

AbstractGrowing evidence has indicated that circular RNAs (circRNAs) play a pivotal role as functional RNAs in diverse cancers. However, most circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined, and the underlying molecular mechanisms mediated by circRNAs are largely unclear. Here, we screened human circRNA expression profiles in ESCC tissues and found significantly increased expression of hsa_circ_0000277 (termed circPDE3B) in ESCC tissues and cell lines compared to the normal controls. Moreover, higher circPDE3B expression in patients with ESCC was correlated with advanced tumor-node-metastasis (TNM) stage and dismal prognosis. Functional experiments demonstrated that circPDE3B promoted the tumorigenesis and metastasis of ESCC cells in vitro and in vivo. Mechanistically, bioinformatics analysis, a dual-luciferase reporter assay, and anti-AGO2 RNA immunoprecipitation showed that circPDE3B could act as a competing endogenous RNA (ceRNA) by harboring miR-4766-5p to eliminate the inhibitory effect on the target gene laminin α1 (LAMA1). In addition, LAMA1 was significantly upregulated in ESCC tissues and was positively associated with the aggressive oncogenic phenotype. More importantly, rescue experiments revealed that the oncogenic role of circPDE3B in ESCC is partly dependent on the miR-4766-5p/LAMA1 axis. Furthermore, bioinformatics analysis combined with validation experiments showed that epithelial-mesenchymal transition (EMT) activation was involved in the oncogenic functions of the circPDE3B–miR-4766-5p/LAMA1 axis in ESCC. Taken together, we demonstrate for the first time that the circPDE3B/miR-4766-5p/LAMA1 axis functions as an oncogenic factor in promoting ESCC cell proliferation, migration, and invasion by inducing EMT, implying its potential prognostic and therapeutic significance in ESCC.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Chunyan Li ◽  
Xiaoyun He ◽  
Zijun Zhang ◽  
Chunhuan Ren ◽  
Mingxing Chu

Abstract Background Long noncoding RNA (lncRNA) has been identified as important regulator in hypothalamic-pituitary-ovarian axis associated with sheep prolificacy. However, little is known of their expression pattern and potential roles in the pineal gland of sheep. Herein, RNA-Seq was used to detect transcriptome expression pattern in pineal gland between follicular phase (FP) and luteal phase (LP) in FecBBB (MM) and FecB++ (ww) STH sheep, respectively, and differentially expressed (DE) lncRNAs and mRNAs associated with reproduction were identified. Results Overall, 135 DE lncRNAs and 1360 DE mRNAs in pineal gland between MM and ww sheep were screened. Wherein, 39 DE lncRNAs and 764 DE mRNAs were identified (FP vs LP) in MM sheep, 96 DE lncRNAs and 596 DE mRNAs were identified (FP vs LP) in ww sheep. Moreover, GO and KEGG enrichment analysis indicated that the targets of DE lncRNAs and DE mRNAs were annotated to multiple biological processes such as phototransduction, circadian rhythm, melanogenesis, GSH metabolism and steroid biosynthesis, which directly or indirectly participate in hormone activities to affect sheep reproductive performance. Additionally, co-expression of lncRNAs-mRNAs and the network construction were performed based on correlation analysis, DE lncRNAs can modulate target genes involved in related pathways to affect sheep fecundity. Specifically, XLOC_466330, XLOC_532771, XLOC_028449 targeting RRM2B and GSTK1, XLOC_391199 targeting STMN1, XLOC_503926 targeting RAG2, XLOC_187711 targeting DLG4 were included. Conclusion All of these differential lncRNAs and mRNAs expression profiles in pineal gland provide a novel resource for elucidating regulatory mechanism underlying STH sheep prolificacy.


Reproduction ◽  
2014 ◽  
Vol 148 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Fulu Dong ◽  
Yuan Zhang ◽  
Fei Xia ◽  
Yi Yang ◽  
Sidong Xiong ◽  
...  

MicroRNAs (miRNAs) are non-coding RNA molecules of about 22 nucleotides that involved in post-transcriptional gene regulation. Evidence indicates that miRNAs play essential roles in endometriosis, pre-eclampsia, infertility and other reproductive system diseases. However, whether miRNAs are involved in recurrent spontaneous abortion (RSA) is unclear. In this work, we analysed the miRNA expression profiles in six pairs of villus or decidua from RSA patients and normal pregnancy (NP) women using a human miRNA microarray. Some of the chip results were confirmed by RT-qPCR. In the villi of RSA patients, expression of hsa-miR-184, hsa-miR-187 and hsa-miR-125b-2 was significantly higher, while expression of hsa-miR-520f, hsa-miR-3175 and hsa-miR-4672 was significantly lower, comparing with those of NP control. As well, a total of five miRNAs (hsa-miR-517c, hsa-miR-519a-1, hsa-miR-522, hsa-miR-520h and hsa-miR-184) were upregulated in the decidua of RSA patients. The target genes of these differentially expressed miRNAs were predicted by miRWalk, and we speculate a network of miRNA regulating RSA by target genes function on adhesion, apoptosis and angiogenesis. Our study may help clarify the molecular mechanisms which are involved in the progression of RSA, and provide a reference for future research.


Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1610
Author(s):  
Mohammad Vatanparast ◽  
Youngjin Park

Solenopsis japonica, as a fire ant species, shows some predatory behavior towards earthworms and woodlice, and preys on the larvae of other ant species by tunneling into a neighboring colony’s brood chamber. This study focused on the molecular response process and gene expression profiles of S. japonica to low (9 °C)-temperature stress in comparison with normal temperature (25 °C) conditions. A total of 89,657 unigenes (the clustered non-redundant transcripts that are filtered from the longest assembled contigs) were obtained, of which 32,782 were annotated in the NR (nonredundant protein) database with gene ontology (GO) terms, gene descriptions, and metabolic pathways. The results were 81 GO subgroups and 18 EggNOG (evolutionary genealogy of genes: Non-supervised Orthologous Groups) keywords. Differentially expressed genes (DEGs) with log2fold change (FC) > 1 and log2FC < −1 with p-value ≤ 0.05 were screened for cold stress temperature. We found 215 unigenes up-regulated and 115 unigenes down-regulated. Comparing transcriptome profiles for differential gene expression resulted in various DE proteins and genes, including fatty acid synthases and lipid metabolism, which have previously been reported to be involved in cold resistance. We verified the RNA-seq data by qPCR on 20 up- and down-regulated DEGs. These findings facilitate the basis for the future understanding of the adaptation mechanisms of S. japonica and the molecular mechanisms underlying the response to low temperatures.


2021 ◽  
Author(s):  
Weihao Chen ◽  
Zhifeng Li ◽  
Wei Sun ◽  
Mingxing Chu

Abstract Background:In sheep, FecB is the essential biomarker of the fertility, previous researches have provided a detailed insight on the regulation involved estrus phase and FecB in the reproductive-related tissues including hypothalamus, pituitary, and ovary. However, as the host of embryo development and connection between the ovary and the uterus, little is known about the interaction between mRNAs and lncRNAs in sheep oviduct. In the present study, RNA-Seq was performed to identify the transcriptomic profiles of mRNAs and lncRNAs in oviduct during estrus phase of sheep with FecBBB/++ genotypes.Results:In total, 21,863 lncRNAs and 43,674 mRNAs were identified, 57 DE lncRNAs and 637 DE mRNAs were revealed in the comparisons between follicular phase and luteal phase, 26 DE lncRNAs and 421 DE lncRNAs were revealed in the comparisons between FecB BB genotype and FecB ++ genotype. Functional enrichment analysis suggested that GO and KEGG terms related to reproduction such as SAGA complex, ATP-binding cassette (ABC), Nestin, and Hippo signalling pathway. DE-interaction network suggested that LNC_018420 maybe the key regulators related to embryo development in sheep oviduct.Conclusion:This was the first study to reveal the transcriptomic profiles of mRNAs and lncRNAs in the oviduct of FecB BB/++ sheep at estrus phase using RNA-Seq. Our findings can provide new understanding on the molecular mechanisms of mRNAs and lncRNAs underlying sheep embryo development and also opening new lines of investigation in sheep reproduction.


Plants ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 47 ◽  
Author(s):  
Oleg Gorshkov ◽  
Tatyana Chernova ◽  
Natalia Mokshina ◽  
Natalia Gogoleva ◽  
Dmitry Suslov ◽  
...  

Phloem fibers are important elements of plant architecture and the target product of many fiber crops. A key stage in fiber development is intrusive elongation, the mechanisms of which are largely unknown. Integrated analysis of miRNA and mRNA expression profiles in intrusivelygrowing fibers obtained by laser microdissection from flax (Linum usitatissimum L.) stem revealed all 124 known flax miRNA from 23 gene families and the potential targets of differentially expressed miRNAs. A comparison of the expression between phloem fibers at different developmental stages, and parenchyma and xylem tissues demonstrated that members of miR159, miR166, miR167, miR319, miR396 families were down-regulated in intrusively growing fibers. Some putative target genes of these miRNA families, such as those putatively encoding growth-regulating factors, an argonaute family protein, and a homeobox-leucine zipper family protein were up-regulated in elongating fibers. miR160, miR169, miR390, and miR394 showed increased expression. Changes in the expression levels of miRNAs and their target genes did not match expectations for the majority of predicted target genes. Taken together, poorly understood intrusive fiber elongation, the key process of phloem fiber development, was characterized from a miRNA-target point of view, giving new insights into its regulation.


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