Small RNAs, Degradome, and Transcriptome Sequencing Provide Insights into Papaya Fruit Ripening Regulated by 1-MCP

As an inhibitor of ethylene receptors, 1-methylcyclopropene (1-MCP) can delay the ripening of papaya. However, improper 1-MCP treatment will cause a rubbery texture in papaya. Understanding of the underlying mechanism is still lacking. In the present work, a comparative sRNA analysis was conducted after different 1-MCP treatments and identified a total of 213 miRNAs, of which 44 were known miRNAs and 169 were novel miRNAs in papaya. Comprehensive functional enrichment analysis indicated that plant hormone signal pathways play an important role in fruit ripening. Through the comparative analysis of sRNAs and transcriptome sequencing, a total of 11 miRNAs and 12 target genes were associated with the ethylene and auxin signaling pathways. A total of 1741 target genes of miRNAs were identified by degradome sequencing, and nine miRNAs and eight miRNAs were differentially expressed under the ethylene and auxin signaling pathways, respectively. The network regulation diagram of miRNAs and target genes during fruit ripening was drawn. The expression of 11 miRNAs and 12 target genes was verified by RT-qPCR. The target gene verification showed that cpa-miR390a and cpa-miR396 target CpARF19-like and CpERF RAP2-12-like, respectively, affecting the ethylene and auxin signaling pathways and, therefore, papaya ripening.

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Identification of Tumorigenic and Prognostic Biomarkers in Colorectal Cancer Based on microRNA Expression Profiles

BioMed Research International ◽

10.1155/2020/7136049 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Yuntao Shi ◽

Yingying Zhuang ◽

Jialing Zhang ◽

Mengxue Chen ◽

Shangnong Wu

Keyword(s):

Target Genes ◽

Cox Regression ◽

Expression Profiles ◽

Survival Rates ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Risk Groups ◽

Normal Mucosa ◽

Microrna Expression ◽

Functional Enrichment

Objective. Although noncoding RNAs, especially the microRNAs, have been found to play key roles in CRC development in intestinal tissue, the specific mechanism of these microRNAs has not been fully understood. Methods. GEO and TCGA database were used to explore the microRNA expression profiles of normal mucosa, adenoma, and carcinoma. And the differential expression genes were selected. Computationally, we built the SVM model and multivariable Cox regression model to evaluate the performance of tumorigenic microRNAs in discriminating the adenomas from normal tissues and risk prediction. Results. In this study, we identified 20 miRNA biomarkers dysregulated in the colon adenomas. The functional enrichment analysis showed that MAPK activity and MAPK cascade were highly enriched by these tumorigenic microRNAs. We also investigated the target genes of the tumorigenic microRNAs. Eleven genes, including PIGF, TPI1, KLF4, RARS, PCBP2, EIF5A, HK2, RAVER2, HMGN1, MAPK6, and NDUFA2, were identified to be frequently targeted by the tumorigenic microRNAs. The high AUC value and distinct overall survival rates between the two risk groups suggested that these tumorigenic microRNAs had the potential of diagnostic and prognostic value in CRC. Conclusions. The present study revealed possible mechanisms and pathways that may contribute to tumorigenesis of CRC, which could not only be used as CRC early detection biomarkers, but also be useful for tumorigenesis mechanism studies.

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miRNA Mediated Noise Making of 3′UTR Mutations in Cancer

Genes ◽

10.3390/genes9110545 ◽

2018 ◽

Vol 9 (11) ◽

pp. 545 ◽

Cited By ~ 5

Author(s):

Wei Wu ◽

Lingxiang Wu ◽

Mengyan Zhu ◽

Ziyu Wang ◽

Min Wu ◽

...

Keyword(s):

Somatic Mutations ◽

Target Genes ◽

Expression Profiles ◽

Tumor Development ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Messenger Rnas ◽

Cellular Functions ◽

Mrna Binding

Somatic mutations in 3′-untranslated regions (3′UTR) do not alter amino acids and are considered to be silent in cancers. We found that such mutations can promote tumor progression by altering microRNA (miRNA) targeting efficiency and consequently affecting miRNA–mRNA interactions. We identified 67,159 somatic mutations located in the 3′UTRs of messenger RNAs (mRNAs) which can alter miRNA–mRNA interactions (functional somatic mutations, funcMutations), and 69.3% of these funcMutations (the degree of energy change > 12 kcal/mol) were identified to significantly promote loss of miRNA-mRNA binding. By integrating mRNA expression profiles of 21 cancer types, we found that the expression of target genes was positively correlated with the loss of absolute affinity level and negatively correlated with the gain of absolute affinity level. Functional enrichment analysis revealed that genes carrying funcMutations were significantly enriched in the MAPK and WNT signaling pathways, and analysis of regulatory modules identified eighteen miRNA modules involved with similar cellular functions. Our findings elucidate a complex relationship between miRNA, mRNA, and mutations, and suggest that 3′UTR mutations may play an important role in tumor development.

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Integrated lncRNA and mRNA Transcriptome Analyses in the Ovary of Cynoglossus semilaevis Reveal Genes and Pathways Potentially Involved in Reproduction

Frontiers in Genetics ◽

10.3389/fgene.2021.671729 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yani Dong ◽

Likang Lyu ◽

Daiqiang Zhang ◽

Jing Li ◽

Haishen Wen ◽

...

Keyword(s):

Signaling Pathways ◽

Target Genes ◽

Enrichment Analysis ◽

Mapk Signaling ◽

Cynoglossus Semilaevis ◽

Gene Set Enrichment Analysis ◽

Functional Enrichment ◽

Biological Processes ◽

Tongue Sole ◽

Oocyte Meiosis

Long non-coding RNAs (lncRNAs) have been reported to be involved in multiple biological processes. However, the roles of lncRNAs in the reproduction of half-smooth tongue sole (Cynoglossus semilaevis) are unclear, especially in the molecular regulatory mechanism driving ovarian development and ovulation. Thus, to explore the mRNA and lncRNA mechanisms regulating reproduction, we collected tongue sole ovaries in three stages for RNA sequencing. In stage IV vs. V, we identified 312 differentially expressed (DE) mRNAs and 58 DE lncRNAs. In stage V vs. VI, we identified 1,059 DE mRNAs and 187 DE lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DE mRNAs were enriched in ECM-receptor interaction, oocyte meiosis and steroid hormone biosynthesis pathways. Furthermore, we carried out gene set enrichment analysis (GSEA) to identify potential reproduction related-pathways additionally, such as fatty metabolism and retinol metabolism. Based on enrichment analysis, DE mRNAs with a potential role in reproduction were selected and classified into six categories, including signal transduction, cell growth and death, immune response, metabolism, transport and catabolism, and cell junction. The interactions of DE lncRNAs and mRNAs were predicted according to antisense, cis-, and trans-regulatory mechanisms. We constructed a competing endogenous RNA (ceRNA) network. Several lncRNAs were predicted to regulate genes related to reproduction including cyp17a1, cyp19a1, mmp14, pgr, and hsd17b1. The functional enrichment analysis of these target genes of lncRNAs revealed that they were involved in several signaling pathways, such as the TGF-beta, Wnt signaling, and MAPK signaling pathways and reproduction related-pathways such as the progesterone-mediated oocyte maturation, oocyte meiosis, and GnRH signaling pathway. RT-qPCR analysis showed that two lncRNAs (XR_522278.2 and XR_522171.2) were mainly expressed in the ovary. Dual-fluorescence in situ hybridization experiments showed that both XR_522278.2 and XR_522171.2 colocalized with their target genes cyp17a1 and cyp19a1, respectively, in the follicular cell layer. The results further demonstrated that lncRNAs might be involved in the biological processes by modulating gene expression. Taken together, this study provides lncRNA profiles in the ovary of tongue sole and further insight into the role of lncRNA involvement in regulating reproduction in tongue sole.

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3131 ONCOSTREAMS: NOVEL DYNAMICS PATHOLOGICAL MULTICELLULAR STRUCTURES INVOLVED IN GLIOBLATOMA GROWTH AND INVASION

Journal of Clinical and Translational Science ◽

10.1017/cts.2019.253 ◽

2019 ◽

Vol 3 (s1) ◽

pp. 111-111 ◽

Cited By ~ 2

Author(s):

Andrea Comba ◽

Patrick Dunn ◽

Anna E Argento ◽

Padma Kadiyala ◽

Sebastien Motsch ◽

...

Keyword(s):

Extracellular Matrix ◽

Target Genes ◽

Collective Motion ◽

Malignant Tumors ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Genetically Engineered ◽

Functional Enrichment ◽

Low Grade ◽

Normal Brain

OBJECTIVES/SPECIFIC AIMS: Oncostreams represent a novel growth pattern of GBM. In this study we uncovered the cellular and molecular mechanism that regulates the oncostreams function in GBM growth and invasion. METHODS/STUDY POPULATION: We studied oncostreams organization and function using genetically engineered mouse gliomas models (GEMM), mouse primary patient derived GBM model and human glioma biopsies. We evaluated the molecular landscape of oncostreams by laser capture microdissection (LCM) followed by RNA-Sequencing and bioinformatics analysis. RESULTS/ANTICIPATED RESULTS: Oncostreams are multicellular structures of 10-20 cells wide and 2-400 μm long. They are distributed throughout the tumors in mouse and human GBM. Oncostreams are heterogeneous structures positive for GFAP, Nestin, Olig2 and Iba1 cells and negative for Neurofilament. Using GEMM we found a negative correlation between oncostream density and animal survival. Moreover, examination of patient’s glioma biopsies evidenced that oncostreams are present in high grade but no in low grade gliomas. This suggests that oncostreams may play a role in tumor malignancy. Our data also indicated that oncostreams aid local invasion of normal brain. Transcriptome analysis of oncostreams revealed 43 differentially expressed (DE) genes. Functional enrichment analysis of DE genes showed that “collagen catabolic processes”, “positive regulation of cell migration”, and “extracellular matrix organization” were the most over-represented GO biological process. Network analysis indicated that Col1a1, ACTA2, MMP9 and MMP10 are primary target genes. These genes were also overexpressed in more malignant tumors (WT-IDH) compared to the less malignant (IDH1- R132H) tumors. Confocal time lapse imagining of 3D tumor slices demonstrated that oncostreams display a collective motion pattern within gliomas that has not been seen before. DISCUSSION/SIGNIFICANCE OF IMPACT: In summary, oncostreams are anatomically and molecularly distinctive, regulate glioma growth and invasion, display collective motion and are regulated by the extracellular matrix. We propose oncostreams as novel pathological markers valuable for diagnosis, prognosis and designing therapeutics for GBM patients.

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Downregulation of miRNA-205 Expression and Biological Mechanism in Prostate Cancer Tumorigenesis and Bone Metastasis

BioMed Research International ◽

10.1155/2020/6037434 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Yu Sun ◽

Sheng-Hua Li ◽

Ji-Wen Cheng ◽

Gang Chen ◽

Zhi-Guang Huang ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastasis ◽

Protein Level ◽

Target Genes ◽

Mrna Level ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Forest Plot ◽

Biological Mechanism

Background. The expression and mechanism of microRNA-205 (miRNA-205) in prostate cancer (PCa) and its bone metastasis remain controversial. Materials and Methods. The expression and discriminating capability of miRNA-205 were assessed by drawing a forest plot and a summarized receiver operating characteristic (SROC) curve, using data available from 27 miRNA-array and miRNA-sequencing datasets. The miRNA-205 target genes were acquired from online prediction tools, differentially upregulated genes in PCa, and differentially expressed genes (DEGs) after miRNA-205 transfection into PCa cell lines. Functional enrichment analysis was conducted to explore the biological mechanism of miRNA-205 targets. Immunohistochemistry (IHC) was applied to verify the protein level of the hub gene. Results. The expression of miRNA-205 in the PCa group (1,461 samples) was significantly lower than that in the noncancer group (510 samples), and the downregulation of miRNA-205 showed excellent sensitivity and specificity in differentiating between the two groups. In bone metastatic PCa, the miRNA-205 level was further reduced than in nonbone metastatic PCa, and it showed a good capability in distinguishing between the two groups. In total, 153 miRNA-205 targets were screened through the three aforementioned methods. Based on the results of functional enrichment analysis, the targets of miRNA-205 were mainly enriched during chromosome segregation and phospholipid-translocating ATPase activity and in the spindle microtubule and the p53 signaling pathway. CDK1 had the highest connectivity in the PPI network analysis and was screened as one of the hub genes. A statistically significant negative correlation between miRNA-205 and CDK1 was observed. The expression of CDK1 in PCa samples was pronouncedly upregulated in terms of both the mRNA level and the protein level when compared with noncancer samples. Conclusion. miRNA-205 may play a vital role in PCa tumorigenesis and bone metastasis by targeting CDK1.

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System Analysis of MIRNAs in Maize Internode Elongation

Biomolecules ◽

10.3390/biom9090417 ◽

2019 ◽

Vol 9 (9) ◽

pp. 417

Author(s):

Chuanxi Peng ◽

Xing Wang ◽

Tianyu Feng ◽

Rui He ◽

Mingcai Zhang ◽

...

Keyword(s):

Target Genes ◽

System Analysis ◽

Interaction Network ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Differentially Expressed ◽

Internode Elongation ◽

Differentially Expressed Mirnas ◽

Post Transcriptional Regulation

MicroRNAs (miRNAs), the post-transcriptional gene regulators, are known to play an important role in plant development. The identification of differentially expressed miRNAs could better help us understand the post-transcriptional regulation that occurs during maize internode elongation. Accordingly, we compared the expression of MIRNAs between fixed internode and elongation internode samples and classified six differentially expressed MIRNAs as internode elongation-responsive miRNAs including zma-MIR160c, zma-MIR164b, zma-MIR164c, zma-MIR168a, zma-MIR396f, and zma-MIR398b, which target mRNAs supported by transcriptome sequencing. Functional enrichment analysis for predictive target genes showed that these miRNAs were involved in the development of internode elongation by regulating the genes respond to hormone signaling. To further reveal how miRNA affects internode elongation by affecting target genes, the miRNA–mRNA–PPI (protein and protein interaction) network was constructed to summarize the interaction of miRNAs and these target genes. Our results indicate that miRNAs regulate internode elongation in maize by targeting genes related to cell expansion, cell wall synthesis, transcription, and regulatory factors.

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Functional Enrichment Analysis by David in Transgenic MYCN Zebrafish Model

Blood ◽

10.1182/blood.v120.21.5114.5114 ◽

2012 ◽

Vol 120 (21) ◽

pp. 5114-5114

Author(s):

Li-Jing Shen ◽

Fang-Yuan Chen ◽

Lan-Fang Cao ◽

Yong Zhang ◽

Hua Zhong

Keyword(s):

Cell Cycle ◽

Signaling Pathways ◽

Microarray Analysis ◽

Conflicts Of Interest ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Mapk Signaling ◽

Functional Enrichment ◽

Tgfβ Signaling ◽

Apoptosis Pathway

Abstract Abstract 5114 Introduction The MYCN oncogene encodes a basic helix-loop-helix/leucine zipper (bHLH/LZ) transcription factor that is frequently overexpressed in hematologic malignancies neoplasms (including acute leukemia, T-cell lymphoma, and so on). MYCN acts as a poor prognostic marker to promote an aggressive phenotype. However, the mechanisms of action and pathways affected by MYCN are still largely unclear. Methods We induced murine MYCN gene overexpression in embryonic zebrafish through heat-shock promoter and established stable germline Tg(MYCN:HSE:EGFP) zebrafish. RNA was extracted at 3 days post fertilization from wild type (WT) and transgenic zebrafish F1 generation (TG) embryo hematopoietic cells, collected by the flow cytometer, for microarray analysis. The samples were processed and subsequently analyzed in triplicate on Zebrafish Oligo Microarrays (Agilent Technologies), containing 43, 554 sets of probe, at the Advanced Throughput Inc. The microarrays were scanned in an Agilent DNA Microarray Scanner and the images were processed using Feature Extraction software. A False Discovery Rate≤0. 05 for overall interactions effect and P<0. 001 between comparisons were used to determine differentially expressed genes (DEG). Ingenuity Pathway Analysis and DAVID performed the functional analysis of DEG. Results Microarray analysis revealed 626 (342 genes up-regulated and 284 genes down-regulated) DEG that showed >2-fold change in TG comparing with that of WT. Using functional enrichment analysis by DAVID, several signaling pathways were regulated in TG samples (Table 1). MAPK signaling pathway was high activated through FGF, PDGF, BDNF and CACN high expression, promoting up-regulated of Ras and MKP, enhancing phosphorylation and leading to increase of cells proliferation. TGFβ signaling was inhibited by up-regulation of IFN Ã and Smad 6/7, which negative control of TGFβR and Smad 2/3. Further, we found that MYCN enhances the expression of skp2, via decreased p21 and increased CDK2, promoting cell cycle progression (Fig. 1). In addition, overexpression of MYCN weakened the function of mismatch repair, base excision repair, while increased apoptosis pathway mediated by p53 (up-regulated Bid gene). Meanwhile, Glycolysis/gluconeogenesis pathway was significantly up-regulated in TG fish. Conclusions Overexpression of MYCN induced up-regulation of cell proliferation and Glycolysis/gluconeogenesis pathway (as the Warburg effect in rapidly proliferating tumors), attenuation of repair function, all of which are phenomena associated with proliferation and malignancies transformation of blood cell feature. We found that MYCN down-regulates p27kip1, p57kip2 and p21cip1 through up-regulate Skp2, thus up-regulates CDK2, CycA, CycB, CycD and CycE. All above changes shortened the time taken to progress through the cell cycle. Increased MARK signaling and decreased TGFβ signaling pathways also contributed to promote cell cycle. (Red star marks the up-regulated genes). Disclosures: No relevant conflicts of interest to declare.

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Molecular characterization of metabolic subtypes of gastric cancer based on metabolism-related lncRNA

Scientific Reports ◽

10.1038/s41598-021-00410-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lingdi Li ◽

Jianfei Ma

Keyword(s):

Gastric Cancer ◽

Metabolic Pathways ◽

Metabolic Regulation ◽

Protective Factor ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Underlying Mechanism ◽

Functional Enrichment ◽

Biological Processes

AbstractIncreasing evidence has demonstrated that lncRNAs are critical regulators in diverse biological processes, but the function of lncRNA in metabolic regulation remains largely unexplored. In this study, we evaluated the association between lncRNA and metabolic pathways and identified metabolism-related lncRNAs. Gastric cancer can be mainly subdivided into 2 clusters based on these metabolism-related lncRNA regulators. Comparative analysis shows that these subtypes are found to be highly consistent with previously identified subtypes based on other omics data. Functional enrichment analysis shows that they are enriched in distinct biological processes. Mutation analysis shows that ABCA13 is a protective factor in subtype C1 but a risk factor in C2. Analysis of chemotherapeutic and immunotherapeutic sensitivity shows that these subtypes tend to display distinct sensitivity to the same chemical drugs. In conclusion, these findings demonstrated the significance of lncRNA in metabolic regulation. These metabolism-related lncRNA regulators can improve our understanding of the underlying mechanism of lncRNAs and advance the research of immunotherapies in the clinical management of gastric cancer.

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Circular RNA screening identifies circMYLK4 as a regulator of fast/slow myofibers in porcine skeletal muscles

10.21203/rs.3.rs-62413/v1 ◽

2020 ◽

Author(s):

Haigang Cao ◽

Jieming Liu ◽

Tianning Du ◽

Yihao Liu ◽

Xiaoyu Zhang ◽

...

Keyword(s):

Muscle Development ◽

Target Genes ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Circular Rna ◽

Functional Enrichment ◽

Differentially Expressed ◽

Marker Genes ◽

Type Conversion ◽

Myofiber Type

Abstract Background: The myofiber type is related to the quality of meat; specifically, slow-oxidized myofiber helps to increase the tenderness and juiciness of meat. An increasing number of studies have shown that circRNAs play a key role in skeletal muscle development. However, the key circRNAs that regulate myofiber types and their roles are still poorly understood.Results: A total of 40757 circRNAs were identified from the longissimus dorsi (LD) and the soleus (Sol) muscles, of which 10388 were co-expressed in the two muscles. Further analysis found 181 differentially expressed circRNAs in the LD compared with Sol. Functional enrichment analysis showed that target genes of differentially expressed circRNA-sponge miRNAs were enriched in the AMPK, FoxO and PI3K-Akt signaling pathways. In addition, we focused on a novel circRNA—circMYLK4. CircMYLK4 significantly increased the mRNA and protein levels of slow muscle marker genes and caused the flesh to turn red.Conclusion: Our study laid an essential foundation for further research on circRNAs in myofiber type conversion and the achievement of higher meat quality.

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Cistrome-GO: a web server for functional enrichment analysis of transcription factor ChIP-seq peaks

Nucleic Acids Research ◽

10.1093/nar/gkz332 ◽

2019 ◽

Vol 47 (W1) ◽

pp. W206-W211 ◽

Cited By ~ 15

Author(s):

Shaojuan Li ◽

Changxin Wan ◽

Rongbin Zheng ◽

Jingyu Fan ◽

Xin Dong ◽

...

Keyword(s):

Gene Expression ◽

Gene Regulation ◽

Transcription Factor ◽

Target Genes ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Differential Gene ◽

Direct Target ◽

Human And Mouse

AbstractCharacterizing the ontologies of genes directly regulated by a transcription factor (TF), can help to elucidate the TF’s biological role. Previously, we developed a widely used method, BETA, to integrate TF ChIP-seq peaks with differential gene expression (DGE) data to infer direct target genes. Here, we provide Cistrome-GO, a website implementation of this method with enhanced features to conduct ontology analyses of gene regulation by TFs in human and mouse. Cistrome-GO has two working modes: solo mode for ChIP-seq peak analysis; and ensemble mode, which integrates ChIP-seq peaks with DGE data. Cistrome-GO is freely available at http://go.cistrome.org/.

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