MicroRNA Expression Profile Analysis of Chlamydomonas reinhardtii during Lipid Accumulation Process under Nitrogen Deprivation Stresses

Lipid accumulation in various microalgae has been found induced by nitrogen deprivation, and it controls many different genes expression. Yet, the underlying molecular mechanisms still remain largely unknown. MicroRNA (miRNAs) play a critical role in post-transcriptional gene regulation. In this study, miRNAs were hypothesized involved in lipid accumulation by nitrogen deprivation. A deep-sequencing platform was used to explore miRNAs-mediated responses induced by nitrogen deprivation in Chlamydomonas reinhardtii. The eukaryotic orthologous groups of proteins (KOG) function in the predicted target genes of miRNA with response to nitrogen deprivation were mainly involved in signal transduction mechanisms, including transcription, lipid transport, and metabolism. A total of 109 miRNA were predicted, including 79 known miRNA and 30 novel miRNA. A total of 29 miRNAs showed significantly differential expressions after nitrogen deprivation, and most of them were upregulated. A total of 10 miRNAs and their targeting genes might involve in lipid transport and metabolism biological process. This study first investigates nitrogen deprivation-regulated miRNAs in microalgae and broadens perspectives on miRNAs importance in microalgae lipid accumulation via nitrogen deprivation. This study provides theoretical guidance for the application of microalgae in bio-oil engineering production.

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STAT3 and STAT5 Activation in Solid Cancers

Cancers ◽

10.3390/cancers11101428 ◽

2019 ◽

Vol 11 (10) ◽

pp. 1428 ◽

Cited By ~ 18

Author(s):

Sebastian Igelmann ◽

Heidi Neubauer ◽

Gerardo Ferbeyre

Keyword(s):

Tumor Suppressor ◽

Molecular Mechanisms ◽

Target Genes ◽

Critical Role ◽

Control Cell ◽

Cytokine Signaling ◽

Specific Gene ◽

Mitochondrial Functions ◽

Context Dependent

The Signal Transducer and Activator of Transcription (STAT)3 and 5 proteins are activated by many cytokine receptors to regulate specific gene expression and mitochondrial functions. Their role in cancer is largely context-dependent as they can both act as oncogenes and tumor suppressors. We review here the role of STAT3/5 activation in solid cancers and summarize their association with survival in cancer patients. The molecular mechanisms that underpin the oncogenic activity of STAT3/5 signaling include the regulation of genes that control cell cycle and cell death. However, recent advances also highlight the critical role of STAT3/5 target genes mediating inflammation and stemness. In addition, STAT3 mitochondrial functions are required for transformation. On the other hand, several tumor suppressor pathways act on or are activated by STAT3/5 signaling, including tyrosine phosphatases, the sumo ligase Protein Inhibitor of Activated STAT3 (PIAS3), the E3 ubiquitin ligase TATA Element Modulatory Factor/Androgen Receptor-Coactivator of 160 kDa (TMF/ARA160), the miRNAs miR-124 and miR-1181, the Protein of alternative reading frame 19 (p19ARF)/p53 pathway and the Suppressor of Cytokine Signaling 1 and 3 (SOCS1/3) proteins. Cancer mutations and epigenetic alterations may alter the balance between pro-oncogenic and tumor suppressor activities associated with STAT3/5 signaling, explaining their context-dependent association with tumor progression both in human cancers and animal models.

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Identification of microRNAs in the green and red sectors of Amaranthus tricolor L. leaves based on Illumina sequencing data

10.7287/peerj.preprints.26723 ◽

2018 ◽

Author(s):

Shengcai Liu ◽

Liyun Peng ◽

Junfei Pan ◽

Xiao Wang ◽

Chunli Zhao ◽

...

Keyword(s):

Illumina Sequencing ◽

Molecular Mechanisms ◽

Target Genes ◽

Sequencing Data ◽

Amaranthus Tricolor ◽

Sequencing Platform ◽

Transcriptome Database ◽

Polymerase Chain ◽

Illumina Sequencing Platform ◽

Illumina Sequencing Data

Betalains are abundant in amaranth plants. Additionally, the betalain molecular structure and metabolic pathway differ from those of betanin in beet plants. To date, only a few studies have examined the regulatory roles of miRNAs in betalain biosynthesis in plants. Thus, we constructed small RNA libraries for the red and green sectors of amaranth leaves to identify miRNAs associated with betalain biosynthesis. We identified 198 known and 41 novel miRNAs. Moreover, 216 miRNAs were distributed in 44 miRNA families, including miR156, miR159, miR160, miR166, miR172, miR319, miR167, miR396, and miR398. An analysis of all unigene sequences in an amaranth transcriptome database resulted in the detection of 493 target genes for the 239 screened miRNAs. The targets included SPL2, ARF18, ARF6, and NAC. A quantitative real-time polymerase chain reaction validation of 20 miRNAs and nine target genes revealed expression-level differences between the red and green sectors of amaranth leaves. This study involved the application of an Illumina sequencing platform to identify miRNAs regulating betalain metabolism in amaranth plants. The data presented herein may provide insights into the molecular mechanisms underlying the regulation of betalain biosynthesis in amaranth and other plant species.

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Role Of Histone Deacetylase 6 (HDAC6) In The Modulation Of STAT Pathways and Immune Function Of APCs

Blood ◽

10.1182/blood.v122.21.1032.1032 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1032-1032

Author(s):

Maritza Lienlaf ◽

Patricio Perez-Villarroel ◽

Fengdong Cheng ◽

Calvin K. Lee ◽

Jorge Canales ◽

...

Keyword(s):

Cell Lines ◽

Histone Deacetylases ◽

Molecular Mechanisms ◽

Target Genes ◽

Conflicts Of Interest ◽

Cell Cycle Control ◽

Critical Role ◽

Histone Deacetylase 6 ◽

Histone Modifiers

Abstract Histone deacetylases (HDACs), originally discovered as histone modifiers are now proposed as important regulators of non-chromatin related processes, including the regulation of cellular pathways involved in the production of anti- and pro-inflammatory cytokines and the subsequent function of antigen-presenting cells (APCs). We have recently identified HDAC6 as a positive regulatory factor in the production of IL-10. However, the participation of this HDAC in other immune related cellular processes remains unknown. In this work we present evidence of the important role of HDAC6 in the modulation of the JAK/STAT pathway through the IL-6 regulation. We generated knockdown cell lines of HDAC6 (HDAC6KD) and non-target (NT) cells as a control in RAW264.7 murine macrophages using lentiviral shRNA. Two HADC6KD and two NT cell lines were treated with LPS or were left untreated and then analyzed by microarray. In HDAC6KD cells we found 1542 genes were down-regulated and 775 up-regulated in HDAC6KD cells. Their ontology distribution revealed significant changes in immune-related and apoptosis/cell cycle control genes. Importantly, we observed that most STAT3 and SP1 target genes were down regulated in HDAC6KD cells, suggesting the participation of HDAC6 in the regulation of these two transcription factors. Further analysis evidenced that the phosphorylation of STAT3 and the acetylation of Sp1 were diminished in HDAC6KD cells when compared against control cells. Chromatin immuneprecipitacion (CHIP) assays indicate that this particular effect of abrogation of HDAC6 involved histone modifications at the IL-6 promoter level, and more importantly, the recruitment of STAT3 and Sp1 to the IL-6 promoter was abrogated. Then, we analyzed the relevance of these findings by studying the tolerogenic JAK/STAT signaling pathway, which is known to be activated by IL-6 and critical in the final outcome of APCs in response to stimuli. Our observations included a complete abrogation in the phosphorylation of JAK2 and STAT3 proteins in HDAC6KD cells in response to LPS, which was reverted when these cells were treated with exogenous IL-6. Our final results demonstrate a critical role of HDAC6 in the modulation of IL-6 and the potential role of HDAC6 in the regulation of the JAK/STAT3 pathway. In addition HDAC6 is a regulator of SP1 and STAT3 target genes. These findings provide insight into the molecular mechanisms controlling the immunogenicity of APCs, supporting the use of HDAC6 inhibitors to enhance immune activation, and positioning HDAC6 as a potential therapeutic target. Disclosures: No relevant conflicts of interest to declare.

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SOX11 target genes: implications for neurogenesis and neuropsychiatric illness

Acta Neuropsychiatrica ◽

10.1111/j.1601-5215.2011.00583.x ◽

2012 ◽

Vol 24 (1) ◽

pp. 16-25 ◽

Cited By ~ 5

Author(s):

Li Sha ◽

Rob Kitchen ◽

David Porteous ◽

Douglas Blackwood ◽

Walter Muir ◽

...

Keyword(s):

Molecular Mechanisms ◽

Target Genes ◽

Critical Role ◽

Hek293 Cells ◽

Neuronal Phenotype ◽

Embryonic Neurogenesis ◽

Transcriptional Changes ◽

Differentiation Stage ◽

Downstream Gene Expression ◽

Sox11 Protein

Objective:Deficits in adult and embryonic neurogenesis have been linked with neurological and psychiatric disorders, so it is important to understand the molecular mechanisms underlying this process. SOX11 is a transcription factor known to play a critical role in the regulation of the neuronal and glial differentiation stage of neurogenesis, so we hypothesised that the identification of its target genes would reveal underlying biological processes relevant to disease.Methods:SOX11 protein was over-expressed in HEK293 cells and transcriptional changes assessed by microarray analysis. Selected candidate genes were further tested for SOX11 activation in quantitative reverse transcriptase PCR studies of HEK293 cells and Western analysis of SH-SY5Y cells.Results:Regulated genes included a previously established SOX11 target, known markers of neurogenesis, as well as several genes implicated in neuropsychiatric disorders. Immunofluorescence localised several of the genes within the proliferative subgranular zone of the hippocampus. We observed multiple histone and zinc finger genes regulated by SOX11, many of which were located in two clusters on chromosomes 6 and 19. The chromosome 6 cluster lies within a region of the genome showing the strongest genetic association with schizophrenia.Conclusion:SOX11 appears to regulate a complex programme of chromatin remodelling and downstream gene expression changes to achieve a mature neuronal phenotype. SOX11 target genes are shown to be involved in neurodevelopmental processes important in health and, potentially, disease.

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Transcription factors IRF8 and PU.1 are required for follicular B cell development and BCL6-driven germinal center responses

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1901258116 ◽

2019 ◽

Vol 116 (19) ◽

pp. 9511-9520 ◽

Cited By ~ 14

Author(s):

Hongsheng Wang ◽

Shweta Jain ◽

Peng Li ◽

Jian-Xin Lin ◽

Jangsuk Oh ◽

...

Keyword(s):

Transcription Factors ◽

B Cells ◽

B Cell ◽

Germinal Center ◽

Molecular Mechanisms ◽

Target Genes ◽

Critical Role ◽

B Cell Lymphoma ◽

Cell Development ◽

Affinity Maturation

The IRF and Ets families of transcription factors regulate the expression of a range of genes involved in immune cell development and function. However, the understanding of the molecular mechanisms of each family member has been limited due to their redundancy and broad effects on multiple lineages of cells. Here, we report that double deletion of floxed Irf8 and Spi1 (encoding PU.1) by Mb1-Cre (designated DKO mice) in the B cell lineage resulted in severe defects in the development of follicular and germinal center (GC) B cells. Class-switch recombination and antibody affinity maturation were also compromised in DKO mice. RNA-seq (sequencing) and ChIP-seq analyses revealed distinct IRF8 and PU.1 target genes in follicular and activated B cells. DKO B cells had diminished expression of target genes vital for maintaining follicular B cell identity and GC development. Moreover, our findings reveal that expression of B-cell lymphoma protein 6 (BCL6), which is critical for development of germinal center B cells, is dependent on IRF8 and PU.1 in vivo, providing a mechanism for the critical role for IRF8 and PU.1 in the development of GC B cells.

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Analyzing the interactions of circRNAs, miRNAs, and mRNAs to predict ceRNA networks in human acute type A aortic dissection

10.21203/rs.2.10144/v1 ◽

2019 ◽

Author(s):

maoxun huang ◽

hulin piao ◽

yong wang ◽

weitie wang ◽

bo li ◽

...

Keyword(s):

Aortic Dissection ◽

Molecular Mechanisms ◽

Target Genes ◽

Critical Role ◽

Type A ◽

Integrated Analysis ◽

Acute Type ◽

Type A Aortic Dissection ◽

Cerna Network ◽

Key Genes

Abstract Background: Acute type A aortic dissection(ATAAD) is a life-threatening vascular disease. However, its underlying mechanism is still not well understood. Here, circular RNAs(circRNAs) were shown to function as competitive endogenous RNAs (ceRNAs) to regulate the effect of microRNAs(miRNAs) on their target genes may play a critical role in ATAAD. However, comprehensive identification and integrated analysis of the circRNA-miRNA-mRNA network in ATAAD have not been performed. Results: The gene expression profile of circRNAs, miRNAs, and mRNAs was performed between 6 ATAAD patients and 6 age-matched normal ascending aortic wall tissues patients were analyzed using the Arraystar human RNAs microarray. We identified that the expression of 12576 circRNAs,1603 miRNAs, and 14596 mRNAs were found to be differentially expressed(DE). Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses(KEGG) were performed on these DE mRNAs and miRNA-mediated target genes of circRNAs. Furthermore, we used a multi-step computational framework and several bioinformatics methods to construct a ceRNA network containing circRNAs, miRNAs, and mRNAs based on co-expression analysis between the DE genes. The constructed ceRNA regulatory network containing 25 circRNAs, 17 miRNAs and 72 mRNAs. In the whole ceRNA network. We identified that plenty of key genes, such as hsa_circRNA_404522, hsa_circRNA_0022920, hsa_circ_0075881, hsa-miRNA1285-3p, hsa-miRNA-1285-3p, hsa-miRNA-637, hsa-miRNA-650, TINAGL1, JPH4, PLXNA2, TGFBR1, and THSD4. Furthermore, we also integrated the circRNA-miRNA-mRNA regulatory modules of the key genes. Conclusions: This study found a profile of dysregulated circRNAs, miRNA and mRNAs, and competitive circRNA-miRNA–mRNA regulatory networks were comprehensively integrated and predicted to be involved in ATAAD by GO and KEGG pathway analysis. It might be prospective clinical markers associated with ATAAD, and it is worthwhile to perform further studies to reveal the underlying link between these key genes and the molecular mechanisms of AD. Keywords：aortic dissection; circRNAs; miRNAs; mRNAs; ceRNA

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Genome-wide identification of CCA1 targets uncovers an expanded clock network in Arabidopsis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1513609112 ◽

2015 ◽

Vol 112 (34) ◽

pp. E4802-E4810 ◽

Cited By ~ 105

Author(s):

Dawn H. Nagel ◽

Colleen J. Doherty ◽

Jose L. Pruneda-Paz ◽

Robert J. Schmitz ◽

Joseph R. Ecker ◽

...

Keyword(s):

Circadian Clock ◽

Stress Responses ◽

Molecular Mechanisms ◽

Target Genes ◽

Critical Role ◽

Gene Promoters ◽

Biological Processes ◽

Functional Studies ◽

Genome Wide ◽

Genomic Regions

The circadian clock in Arabidopsis exerts a critical role in timing multiple biological processes and stress responses through the regulation of up to 80% of the transcriptome. As a key component of the clock, the Myb-like transcription factor CIRCADIAN CLOCK ASSOCIATED1 (CCA1) is able to initiate and set the phase of clock-controlled rhythms and has been shown to regulate gene expression by binding directly to the evening element (EE) motif found in target gene promoters. However, the precise molecular mechanisms underlying clock regulation of the rhythmic transcriptome, specifically how clock components connect to clock output pathways, is poorly understood. In this study, using ChIP followed by deep sequencing of CCA1 in constant light (LL) and diel (LD) conditions, more than 1,000 genomic regions occupied by CCA1 were identified. CCA1 targets are enriched for a myriad of biological processes and stress responses, providing direct links to clock-controlled pathways and suggesting that CCA1 plays an important role in regulating a large subset of the rhythmic transcriptome. Although many of these target genes are evening expressed and contain the EE motif, a significant subset is morning phased and enriched for previously unrecognized motifs associated with CCA1 function. Furthermore, this work revealed several CCA1 targets that do not cycle in either LL or LD conditions. Together, our results emphasize an expanded role for the clock in regulating a diverse category of genes and key pathways in Arabidopsis and provide a comprehensive resource for future functional studies.

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ASPP2 inhibits tumor growth by repressing the mevalonate pathway in hepatocellular carcinoma

Cell Death and Disease ◽

10.1038/s41419-019-2054-7 ◽

2019 ◽

Vol 10 (11) ◽

Cited By ~ 2

Author(s):

Beibei Liang ◽

Rui Chen ◽

Shaohua Song ◽

Hao Wang ◽

Guowei Sun ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Growth ◽

Target Genes ◽

Mevalonate Pathway ◽

Profile Analysis ◽

Critical Role ◽

Inhibitory Effect ◽

Key Enzymes ◽

Chemotherapy Drugs

Abstract Cancer is, fundamentally, a disorder of cell growth and proliferation, which requires adequate supplies of energy and nutrients. In this study, we report that the haplo-insufficient tumor suppressor ASPP2, a p53 activator, negatively regulates the mevalonate pathway to mediate its inhibitory effect on tumor growth in hepatocellular carcinoma (HCC). Gene expression profile analysis revealed that the expression of key enzymes in the mevalonate pathway were increased when ASPP2 was downregulated. HCC cells gained higher cholesterol levels and enhanced tumor-initiating capability in response to the depletion of ASPP2. Simvastatin, a mevalonate pathway inhibitor, efficiently abrogated ASPP2 depletion-induced anchorage-independent cell proliferation, resistance to chemotherapy drugs in vitro, and tumor growth in xenografted nude mice. Mechanistically, ASPP2 interacts with SREBP-2 in the nucleus and restricts the transcriptional activity of SREBP-2 on its target genes, which include key enzymes involved in the mevalonate pathway. Moreover, clinical data revealed better prognosis in patients with high levels of ASPP2 and low levels of the mevalonate pathway enzyme HMGCR. Our findings provide functional and mechanistic insights into the critical role of ASPP2 in the regulation of the mevalonate pathway and the importance of this pathway in tumor initiation and tumor growth, which may provide a new therapeutic opportunity for HCC.

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The molecular basis of progesterone receptor action in breast carcinogenesis

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2011-0129 ◽

2012 ◽

Vol 9 (2) ◽

Cited By ~ 1

Author(s):

Patricia V. Elizalde ◽

Cecilia J. Proietti

Keyword(s):

Breast Cancer ◽

Mammary Gland ◽

Progesterone Receptor ◽

Transcriptional Control ◽

Molecular Mechanisms ◽

Target Genes ◽

Critical Role ◽

Regulatory Elements ◽

Control Of Gene Expression ◽

Receptor Modulation

AbstractProgesterone plays an essential role in the regulation of cell proliferation and differentiation in the mammary gland. In addition, experimental and clinical evidence points to a critical role of progesterone and the nuclear progesterone receptor (PR) in controlling mammary gland tumorigenesis. However, the molecular mechanisms of progesterone action in breast cancer still remain elusive. In its classical mechanism of action, PR acts as a ligand-induced transcription factor (TF) interacting directly with specific progesterone response elements (PREs) in the promoter of target genes. In addition to its transcriptional effects, PR activates signal transduction pathways through a rapid or non-genomic mechanism. Interestingly, progestin induces the expression of key genes involved in breast cancer growth, which lack PREs in their promoters, via a non-classical PR transcriptional mechanism through PR tethering to other TFs. Recent findings on steroid hormone receptor modulation of target genes raise the most exciting possibility that progestin may also induce long-range transcriptional control of gene expression via PR binding to cis-regulatory elements (PREs or half PREs) located far upstream or downstream from the trascriptional start site. This review will focus on the involvement and interplay of the different PR actions in breast cancer.

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