scholarly journals gga-miRNA-18b-3p Inhibits Intramuscular Adipocytes Differentiation in Chicken by Targeting the ACOT13 Gene

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 556 ◽  
Author(s):  
Guirong Sun ◽  
Fang Li ◽  
Xiangfei Ma ◽  
Junwei Sun ◽  
Ruirui Jiang ◽  
...  

Intramuscular fat (IMF) is the most important evaluating indicator of chicken meat quality, the content of which is positively correlated with tenderness, flavor, and succulence of the meat. Chicken IMF deposition process is regulated by many factors, including genetic, nutrition, and environment. Although large number of omics’ studies focused on the IMF deposition process, the molecular mechanism of chicken IMF deposition is still poorly understood. In order to study the role of miRNAs in chicken intramuscular adipogenesis, the intramuscular adipocyte differentiation model (IMF-preadipocytes and IMF-adipocytes) was established and subject to miRNA-Seq. A total of 117 differentially expressed miRNAs between two groups were obtained. Target genes prediction and functional enrichment analysis revealed that eight pathways involved in lipid metabolism related processes, such as fatty acid metabolism and fatty acid elongation. Meanwhile a putative miRNA, gga-miR-18b-3p, was identified be served a function in the intramuscular adipocyte differentiation. Luciferase assay suggested that the gga-miR-18b-3p targeted to the 3′UTR of ACOT13. Subsequent functional experiments demonstrated that gga-miR-18b-3p acted as an inhibitor of intramuscular adipocyte differentiation by targeting ACOT13. Our findings laid a new theoretical foundation for the study of lipid metabolism, and also provided a potential target to improve the meat quality in the poultry industry.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xingbo Bian ◽  
Pengcheng Yu ◽  
Ling Dong ◽  
Yan Zhao ◽  
He Yang ◽  
...  

AbstractGinseng rusty root symptom (GRS) is one of the primary diseases of ginseng. It leads to a severe decline in the quality of ginseng and significantly affects the ginseng industry. The regulatory mechanism of non-coding RNA (ncRNA) remains unclear in the course of disease. This study explored the long ncRNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) in GRS tissues and healthy ginseng (HG) tissues and performed functional enrichment analysis of the screened differentially expressed ncRNAs. Considering the predictive and regulatory effects of ncRNAs on mRNAs, we integrated ncRNA and mRNA data to analyze and construct relevant regulatory networks. A total of 17,645 lncRNAs, 245 circRNAs, and 299 miRNAs were obtained from HG and GRS samples, and the obtained ncRNAs were characterized, including the classification of lncRNAs, length and distribution of circRNA, and the length and family affiliations of miRNAs. In the analysis of differentially expressed ncRNA target genes, we found that lncRNAs may be involved in the homeostatic process of ginseng tissues and that lncRNAs, circRNAs, and miRNAs are involved in fatty acid-related regulation, suggesting that alterations in fatty acid-related pathways may play a key role in GRS. Besides, differentially expressed ncRNAs play an essential role in regulating transcriptional translation processes, primary metabolism such as starch and sucrose, and secondary metabolism such as alkaloids in ginseng tissues. Finally, we integrated the correlations between ncRNAs and mRNAs, constructed corresponding interaction networks, and identified ncRNAs that may play critical roles in GRS. These results provide a basis for revealing GRS's molecular mechanism and enrich our understanding of ncRNAs in ginseng.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fuhui Han ◽  
Lisheng Zhou ◽  
Le Zhao ◽  
Lei Wang ◽  
Lirong Liu ◽  
...  

Intramuscular fat (IMF) is one of the most critical parameters affecting meat quality and mainly affected by genetic factors. MicroRNA as an important regulatory factor, which is still a lack of research in the development of sheep IMF deposition. We used RNA sequencing (RNA-seq) and cell-level validation to explore the role of miRNA in IMF deposition. As for this purpose, longissimus thoracis et lumborum (LTL) samples of 2 month-old (Mth-2) and 12 months-old (Mth-12) Aohan fine-wool sheep (AFWS) were used to identified miRNAs expression. We found 59 differentially expressed miRNAs (DE-miRNA) between these age groups and predicted their 1,796 target genes. KEGG functional enrichment analysis revealed eight pathways involved in lipid metabolism-related processes, including fatty acid elongation and the AMPK signaling pathway. A highly expressed DE-miRNA, miR-193a-5p, was found to serve a function in 3T3-L1 preadipocyte differentiation. Luciferase assay demonstrated that miR-193a-5p directly binds to the 3′-UTR region of ACAA2. By constructing mimics and inhibitor vector transfecting into 3T3-L1 cells to explore the effect of miR-193a-5p on cell proliferation and differentiation, we demonstrated that overexpression of miR-193a-5p inhibited 3T3-L1 preadipocyte proliferation, as evidenced by decreased mRNA and protein expression of CDK4 and CyclinB. CCK-8 assay showed that miR-193a-5p significantly inhibited cell proliferation. Similarly, the overexpression of miR-193a-5p inhibited 3T3-L1 preadipocyte differentiation and adipocyte-specific molecular markers’ expression, leading to a decrease in PPARγ and C/EBPα and ACAA2. Inhibition of miR-193a-5p had the opposite effects. Our study lists the miRNAs associated with intramuscular lipid deposition in sheep and their potential targets, striving to improve sheep meat quality.


2018 ◽  
Vol 46 (6) ◽  
pp. 2421-2433 ◽  
Author(s):  
Meng Zhang ◽  
Dong-Hua Li ◽  
Fang Li ◽  
Jun-Wei Sun ◽  
Rui-Rui Jiang ◽  
...  

Background/Aims: Poultry meat quality is affected by many factors, among which intramuscular fat (IMF) is predominant. IMF content affects the tenderness, juiciness, and favor of chicken. An increasing number of studies are focusing on the functions of microRNAs (miRNAs) during the adipogenic process. However, little is known about miRNAs associated with poultry IMF deposition, especially intramuscular adipocyte differentiation. Methods: The IMF content of two physiological stages was measured, and miRNA-Seq and RNA-Seq data were integrated and analyzed. A chicken intramuscular adipocyte cell differentiation model was constructed. A luciferase reporter assay, miRNA overexpression, and Oil Red O staining were used to confirm the targets of gga-miR-140-5p. Results: Our results showed that late-laying-period hens, which had a higher IMF content, exhibited lower global expression levels of miRNAs than juvenile hens. A total of 104 differentially expressed (DE) miRNAs were identified between the two groups. Integrated analysis of differentially expressed genes and DE miRNAs identified a total of 378 miRNA-mRNA pairs. Functional enrichment analysis revealed that these intersecting genes are involved in ubiquitin-mediated proteolysis, the peroxisome proliferator-activated receptor signaling pathway, glycerophospholipid metabolism, and fatty acid elongation and degradation pathways. Furthermore, we demonstrated that gga-miR-140-5p promoted intramuscular adipocyte differentiation via targeting retinoid X receptor gamma. Conclusion: Our findings may contribute to a more thorough understanding of chicken IMF deposition and the improvement of poultry meat quality.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pusheng Quan ◽  
Kai Wang ◽  
Shi Yan ◽  
Shirong Wen ◽  
Chengqun Wei ◽  
...  

AbstractThis study aimed to identify potential novel drug candidates and targets for Parkinson’s disease. First, 970 genes that have been reported to be related to PD were collected from five databases, and functional enrichment analysis of these genes was conducted to investigate their potential mechanisms. Then, we collected drugs and related targets from DrugBank, narrowed the list by proximity scores and Inverted Gene Set Enrichment analysis of drug targets, and identified potential drug candidates for PD treatment. Finally, we compared the expression distribution of the candidate drug-target genes between the PD group and the control group in the public dataset with the largest sample size (GSE99039) in Gene Expression Omnibus. Ten drugs with an FDR < 0.1 and their corresponding targets were identified. Some target genes of the ten drugs significantly overlapped with PD-related genes or already known therapeutic targets for PD. Nine differentially expressed drug-target genes with p < 0.05 were screened. This work will facilitate further research into the possible efficacy of new drugs for PD and will provide valuable clues for drug design.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuntao Shi ◽  
Yingying Zhuang ◽  
Jialing Zhang ◽  
Mengxue Chen ◽  
Shangnong Wu

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.


Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 545 ◽  
Author(s):  
Wei Wu ◽  
Lingxiang Wu ◽  
Mengyan Zhu ◽  
Ziyu Wang ◽  
Min Wu ◽  
...  

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yani Dong ◽  
Likang Lyu ◽  
Daiqiang Zhang ◽  
Jing Li ◽  
Haishen Wen ◽  
...  

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.


2019 ◽  
Vol 3 (s1) ◽  
pp. 111-111 ◽  
Author(s):  
Andrea Comba ◽  
Patrick Dunn ◽  
Anna E Argento ◽  
Padma Kadiyala ◽  
Sebastien Motsch ◽  
...  

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.


2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Yu Sun ◽  
Sheng-Hua Li ◽  
Ji-Wen Cheng ◽  
Gang Chen ◽  
Zhi-Guang Huang ◽  
...  

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.


Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 417
Author(s):  
Chuanxi Peng ◽  
Xing Wang ◽  
Tianyu Feng ◽  
Rui He ◽  
Mingcai Zhang ◽  
...  

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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