International Journal of Molecular Sciences

Editorial

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5 pages, 188 KiB

Open AccessEditorial

Transcriptional Regulation: Molecules, Involved Mechanisms, and Misregulation

by Amelia Casamassimi and Alfredo Ciccodicola

Int. J. Mol. Sci. 2019, 20(6), 1281; https://doi.org/10.3390/ijms20061281 - 14 Mar 2019

Cited by 35 | Viewed by 5590

Abstract

Transcriptional regulation is a critical biological process that allows the cell or an organism to respond to a variety of intra- and extra-cellular signals, to define cell identity during development, to maintain it throughout its lifetime, and to coordinate cellular activity [...] Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

Research

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20 pages, 7069 KiB

Open AccessArticle

Global Transcriptional Insights of Pollen-Pistil Interactions Commencing Self-Incompatibility and Fertilization in Tea [Camellia sinensis (L.) O. Kuntze]

by Romit Seth, Abhishek Bhandawat, Rajni Parmar, Pradeep Singh, Sanjay Kumar and Ram Kumar Sharma

Int. J. Mol. Sci. 2019, 20(3), 539; https://doi.org/10.3390/ijms20030539 - 28 Jan 2019

Cited by 31 | Viewed by 7354

Abstract

This study explicates molecular insights commencing Self-Incompatibility (SI) and CC (cross-compatibility/fertilization) in self (SP) and cross (CP) pollinated pistils of tea. The fluorescence microscopy analysis revealed ceased/deviated pollen tubes in SP, while successful fertilization occurred in CP at 48 HAP. Global transcriptome sequencing [...] Read more.

This study explicates molecular insights commencing Self-Incompatibility (SI) and CC (cross-compatibility/fertilization) in self (SP) and cross (CP) pollinated pistils of tea. The fluorescence microscopy analysis revealed ceased/deviated pollen tubes in SP, while successful fertilization occurred in CP at 48 HAP. Global transcriptome sequencing of SP and CP pistils generated 109.7 million reads with overall 77.9% mapping rate to draft tea genome. Furthermore, concatenated de novo assembly resulted into 48,163 transcripts. Functional annotations and enrichment analysis (KEGG & GO) resulted into 3793 differentially expressed genes (DEGs). Among these, de novo and reference-based expression analysis identified 195 DEGs involved in pollen-pistil interaction. Interestingly, the presence of 182 genes [PT germination & elongation (67), S-locus (11), fertilization (43), disease resistance protein (30) and abscission (31)] in a major hub of the protein-protein interactome network suggests a complex signaling cascade commencing SI/CC. Furthermore, tissue-specific qRT-PCR analysis affirmed the localized expression of 42 DE putative key candidates in stigma-style and ovary, and suggested that LSI initiated in style and was sustained up to ovary with the active involvement of csRNS, SRKs & SKIPs during SP. Nonetheless, COBL10, RALF, FERONIA-rlk, LLG and MAPKs were possibly facilitating fertilization. The current study comprehensively unravels molecular insights of phase-specific pollen-pistil interaction during SI and fertilization, which can be utilized to enhance breeding efficiency and genetic improvement in tea. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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16 pages, 2590 KiB

Open AccessCommunication

In Silico Analysis of Pacific Oyster (Crassostrea gigas) Transcriptome over Developmental Stages Reveals Candidate Genes for Larval Settlement

by Valentin Foulon, Pierre Boudry, Sébastien Artigaud, Fabienne Guérard and Claire Hellio

Int. J. Mol. Sci. 2019, 20(1), 197; https://doi.org/10.3390/ijms20010197 - 8 Jan 2019

Cited by 23 | Viewed by 5816

Abstract

Following their planktonic phase, the larvae of benthic marine organisms must locate a suitable habitat to settle and metamorphose. For oysters, larval adhesion occurs at the pediveliger stage with the secretion of a proteinaceous bioadhesive produced by the foot, a specialized and ephemeral [...] Read more.

Following their planktonic phase, the larvae of benthic marine organisms must locate a suitable habitat to settle and metamorphose. For oysters, larval adhesion occurs at the pediveliger stage with the secretion of a proteinaceous bioadhesive produced by the foot, a specialized and ephemeral organ. Oyster bioadhesive is highly resistant to proteomic extraction and is only produced in very low quantities, which explains why it has been very little examined in larvae to date. In silico analysis of nucleic acid databases could help to identify genes of interest implicated in settlement. In this work, the publicly available transcriptome of Pacific oyster Crassostrea gigas over its developmental stages was mined to select genes highly expressed at the pediveliger stage. Our analysis revealed 59 sequences potentially implicated in adhesion of C. gigas larvae. Some related proteins contain conserved domains already described in other bioadhesives. We propose a hypothetic composition of C. gigas bioadhesive in which the protein constituent is probably composed of collagen and the von Willebrand Factor domain could play a role in adhesive cohesion. Genes coding for enzymes implicated in DOPA chemistry were also detected, indicating that this modification is also potentially present in the adhesive of pediveliger larvae. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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14 pages, 1556 KiB

Open AccessArticle

Pax3 Gene Regulated Melanin Synthesis by Tyrosinase Pathway in Pteria penguin

by Feifei Yu, Bingliang Qu, Dandan Lin, Yuewen Deng, Ronglian Huang and Zhiming Zhong

Int. J. Mol. Sci. 2018, 19(12), 3700; https://doi.org/10.3390/ijms19123700 - 22 Nov 2018

Cited by 22 | Viewed by 4587

Abstract

The paired-box 3 (Pax3) is a transcription factor and it plays an important part in melanin synthesis. In this study, a new Pax3 gene was identified from Pteria penguin (Röding, 1798) (P. penguin) by RACE-PCR (rapid-amplification [...] Read more.

The paired-box 3 (Pax3) is a transcription factor and it plays an important part in melanin synthesis. In this study, a new Pax3 gene was identified from Pteria penguin (Röding, 1798) (P. penguin) by RACE-PCR (rapid-amplification of cDNA ends-polymerase chain reaction) and its effect on melanin synthesis was deliberated by RNA interference (RNAi). The cDNA of PpPax3 was 2250 bp long, containing an open reading fragment of 1365 bp encoding 455 amino acids. Amino acid alignment and phylogenetic tree showed PpPax3 shared the highest (69.2%) identity with Pax3 of Mizuhopecten yessoensis. Tissue expression profile showed that PpPax3 had the highest expression in mantle, a nacre-formation related tissue. The PpPax3 silencing significantly inhibited the expression of PpPax3, PpMitf, PpTyr and PpCdk2, genes involved in Tyr-mediated melanin synthesis, but had no effect on PpCreb2 and an increase effect on PpBcl2. Furthermore, the PpPax3 knockdown obviously decreased the tyrosinase activity, the total content of eumelanin and the proportion of PDCA (pyrrole-2,3-dicarboxylic acid) in eumelanin, consistent with influence of tyrosinase (Tyr) knockdown. These data indicated that PpPax3 played an important regulating role in melanin synthesis by Tyr pathway in P. penguin. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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15 pages, 7358 KiB

Open AccessArticle

Causal Transcription Regulatory Network Inference Using Enhancer Activity as a Causal Anchor

by Deepti Vipin, Lingfei Wang, Guillaume Devailly, Tom Michoel and Anagha Joshi

Int. J. Mol. Sci. 2018, 19(11), 3609; https://doi.org/10.3390/ijms19113609 - 15 Nov 2018

Cited by 4 | Viewed by 4277

Abstract

Transcription control plays a crucial role in establishing a unique gene expression signature for each of the hundreds of mammalian cell types. Though gene expression data have been widely used to infer cellular regulatory networks, existing methods mainly infer correlations rather than causality. [...] Read more.

Transcription control plays a crucial role in establishing a unique gene expression signature for each of the hundreds of mammalian cell types. Though gene expression data have been widely used to infer cellular regulatory networks, existing methods mainly infer correlations rather than causality. We developed statistical models and likelihood-ratio tests to infer causal gene regulatory networks using enhancer RNA (eRNA) expression information as a causal anchor and applied the framework to eRNA and transcript expression data from the FANTOM Consortium. Predicted causal targets of transcription factors (TFs) in mouse embryonic stem cells, macrophages and erythroblastic leukaemia overlapped significantly with experimentally-validated targets from ChIP-seq and perturbation data. We further improved the model by taking into account that some TFs might act in a quantitative, dosage-dependent manner, whereas others might act predominantly in a binary on/off fashion. We predicted TF targets from concerted variation of eRNA and TF and target promoter expression levels within a single cell type, as well as across multiple cell types. Importantly, TFs with high-confidence predictions were largely different between these two analyses, demonstrating that variability within a cell type is highly relevant for target prediction of cell type-specific factors. Finally, we generated a compendium of high-confidence TF targets across diverse human cell and tissue types. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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20 pages, 3404 KiB

Open AccessArticle

Role of Overexpressed Transcription Factor FOXO1 in Fatal Cardiovascular Septal Defects in Patau Syndrome: Molecular and Therapeutic Strategies

by Adel Abuzenadah, Saad Alsaedi, Sajjad Karim and Mohammed Al-Qahtani

Int. J. Mol. Sci. 2018, 19(11), 3547; https://doi.org/10.3390/ijms19113547 - 10 Nov 2018

Cited by 11 | Viewed by 8786

Abstract

Patau Syndrome (PS), characterized as a lethal disease, allows less than 15% survival over the first year of life. Most deaths owe to brain and heart disorders, more so due to septal defects because of altered gene regulations. We ascertained the cytogenetic basis [...] Read more.

Patau Syndrome (PS), characterized as a lethal disease, allows less than 15% survival over the first year of life. Most deaths owe to brain and heart disorders, more so due to septal defects because of altered gene regulations. We ascertained the cytogenetic basis of PS first, followed by molecular analysis and docking studies. Thirty-seven PS cases were referred from the Department of Pediatrics, King Abdulaziz University Hospital to the Center of Excellence in Genomic Medicine Research, Jeddah during 2008 to 2018. Cytogenetic analyses were performed by standard G-band method and trisomy13 were found in all the PS cases. Studies have suggested that genes of chromosome 13 and other chromosomes are associated with PS. We, therefore, did molecular pathway analysis, gene interaction, and ontology studies to identify their associations. Genomic analysis revealed important chr13 genes such as FOXO1, Col4A1, HMGBB1, FLT1, EFNB2, EDNRB, GAS6, TNFSF1, STARD13, TRPC4, TUBA3C, and TUBA3D, and their regulatory partners on other chromosomes associated with cardiovascular disorders, atrial and ventricular septal defects. There is strong indication of involving FOXO1 (Forkhead Box O1) gene—a strong transcription factor present on chr13, interacting with many septal defects link genes. The study was extended using molecular docking to find a potential drug lead for overexpressed FOXO1 inhibition. The phenothiazine and trifluoperazine showed efficiency to inhibit overexpressed FOXO1 protein, and could be potential drugs for PS/trisomy13 after validation. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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13 pages, 3894 KiB

Open AccessArticle

PWCDA: Path Weighted Method for Predicting circRNA-Disease Associations

by Xiujuan Lei, Zengqiang Fang, Luonan Chen and Fang-Xiang Wu

Int. J. Mol. Sci. 2018, 19(11), 3410; https://doi.org/10.3390/ijms19113410 - 31 Oct 2018

Cited by 83 | Viewed by 4827

Abstract

CircRNAs have particular biological structure and have proven to play important roles in diseases. It is time-consuming and costly to identify circRNA-disease associations by biological experiments. Therefore, it is appealing to develop computational methods for predicting circRNA-disease associations. In this study, we propose [...] Read more.

CircRNAs have particular biological structure and have proven to play important roles in diseases. It is time-consuming and costly to identify circRNA-disease associations by biological experiments. Therefore, it is appealing to develop computational methods for predicting circRNA-disease associations. In this study, we propose a new computational path weighted method for predicting circRNA-disease associations. Firstly, we calculate the functional similarity scores of diseases based on disease-related gene annotations and the semantic similarity scores of circRNAs based on circRNA-related gene ontology, respectively. To address missing similarity scores of diseases and circRNAs, we calculate the Gaussian Interaction Profile (GIP) kernel similarity scores for diseases and circRNAs, respectively, based on the circRNA-disease associations downloaded from circR2Disease database (http://bioinfo.snnu.edu.cn/CircR2Disease/). Then, we integrate disease functional similarity scores and circRNA semantic similarity scores with their related GIP kernel similarity scores to construct a heterogeneous network made up of three sub-networks: disease similarity network, circRNA similarity network and circRNA-disease association network. Finally, we compute an association score for each circRNA-disease pair based on paths connecting them in the heterogeneous network to determine whether this circRNA-disease pair is associated. We adopt leave one out cross validation (LOOCV) and five-fold cross validations to evaluate the performance of our proposed method. In addition, three common diseases, Breast Cancer, Gastric Cancer and Colorectal Cancer, are used for case studies. Experimental results illustrate the reliability and usefulness of our computational method in terms of different validation measures, which indicates PWCDA can effectively predict potential circRNA-disease associations. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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17 pages, 6759 KiB

Open AccessArticle

PR/SET Domain Family and Cancer: Novel Insights from The Cancer Genome Atlas

by Anna Sorrentino, Antonio Federico, Monica Rienzo, Patrizia Gazzerro, Maurizio Bifulco, Alfredo Ciccodicola, Amelia Casamassimi and Ciro Abbondanza

Int. J. Mol. Sci. 2018, 19(10), 3250; https://doi.org/10.3390/ijms19103250 - 19 Oct 2018

Cited by 38 | Viewed by 5066

Abstract

The PR/SET domain gene family (PRDM) encodes 19 different transcription factors that share a subtype of the SET domain [Su(var)3-9, enhancer-of-zeste and trithorax] known as the PRDF1-RIZ (PR) homology domain. This domain, with its potential methyltransferase activity, is followed by a variable number [...] Read more.

The PR/SET domain gene family (PRDM) encodes 19 different transcription factors that share a subtype of the SET domain [Su(var)3-9, enhancer-of-zeste and trithorax] known as the PRDF1-RIZ (PR) homology domain. This domain, with its potential methyltransferase activity, is followed by a variable number of zinc-finger motifs, which likely mediate protein–protein, protein–RNA, or protein–DNA interactions. Intriguingly, almost all PRDM family members express different isoforms, which likely play opposite roles in oncogenesis. Remarkably, several studies have described alterations in most of the family members in malignancies. Here, to obtain a pan-cancer overview of the genomic and transcriptomic alterations of PRDM genes, we reanalyzed the Exome- and RNA-Seq public datasets available at The Cancer Genome Atlas portal. Overall, PRDM2, PRDM3/MECOM, PRDM9, PRDM16 and ZFPM2/FOG2 were the most mutated genes with pan-cancer frequencies of protein-affecting mutations higher than 1%. Moreover, we observed heterogeneity in the mutation frequencies of these genes across tumors, with cancer types also reaching a value of about 20% of mutated samples for a specific PRDM gene. Of note, ZFPM1/FOG1 mutations occurred in 50% of adrenocortical carcinoma patients and were localized in a hotspot region. These findings, together with OncodriveCLUST results, suggest it could be putatively considered a cancer driver gene in this malignancy. Finally, transcriptome analysis from RNA-Seq data of paired samples revealed that transcription of PRDMs was significantly altered in several tumors. Specifically, PRDM12 and PRDM13 were largely overexpressed in many cancers whereas PRDM16 and ZFPM2/FOG2 were often downregulated. Some of these findings were also confirmed by real-time-PCR on primary tumors. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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14 pages, 4497 KiB

Open AccessArticle

A G-Quadruplex Structure in the Promoter Region of CLIC4 Functions as a Regulatory Element for Gene Expression

by Mu-Ching Huang, I-Te Chu, Zi-Fu Wang, Steven Lin, Ta-Chau Chang and Chin-Tin Chen

Int. J. Mol. Sci. 2018, 19(9), 2678; https://doi.org/10.3390/ijms19092678 - 10 Sep 2018

Cited by 11 | Viewed by 4604

Abstract

The differential transcriptional expression of CLIC4 between tumor cells and the surrounding stroma during cancer progression has been suggested to have a tumor-promoting effect. However, little is known about the transcriptional regulation of CLIC4. To better understand how this gene is regulated, [...] Read more.

The differential transcriptional expression of CLIC4 between tumor cells and the surrounding stroma during cancer progression has been suggested to have a tumor-promoting effect. However, little is known about the transcriptional regulation of CLIC4. To better understand how this gene is regulated, the promoter region of CLIC4 was analyzed. We found that a high GC content near the transcriptional start site (TSS) might form an alternative G-quadruplex (G4) structure. Nuclear magnetic resonance spectroscopy (NMR) confirmed their formation in vitro. The reporter assay showed that one of the G4 structures exerted a regulatory role in gene transcription. When the G4-forming sequence was mutated to disrupt the G4 structure, the transcription activity dropped. To examine whether this G4 structure actually has an influence on gene transcription in the chromosome, we utilized the CRISPR/Cas9 system to edit the G4-forming sequence within the CLIC4 promoter in the cell genome. The pop-in/pop-out strategy was adopted to isolate the precisely-edited A375 cell clone. In CRISPR-modified A375 cell clones whose G4 was disrupted, there was a decrease in the endogenous CLIC4 messenger RNA (mRNA) expression level. In conclusion, we found that the G4 structure in the CLIC4 promoter might play an important role in regulating the level of transcription. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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19 pages, 3360 KiB

Open AccessArticle

Transcriptome Analysis of Novosphingobium pentaromativorans US6-1 Reveals the Rsh Regulon and Potential Molecular Mechanisms of N-acyl-l-homoserine Lactone Accumulation

by Hang Lu and Yili Huang

Int. J. Mol. Sci. 2018, 19(9), 2631; https://doi.org/10.3390/ijms19092631 - 5 Sep 2018

Cited by 9 | Viewed by 3969

Abstract

In most bacteria, a bifunctional Rsh responsible for (p)ppGpp metabolism is the key player in stringent response. To date, no transcriptome-wide study has been conducted to investigate the Rsh regulon, and the molecular mechanism of how Rsh affects the accumulation of N-acyl- [...] Read more.

In most bacteria, a bifunctional Rsh responsible for (p)ppGpp metabolism is the key player in stringent response. To date, no transcriptome-wide study has been conducted to investigate the Rsh regulon, and the molecular mechanism of how Rsh affects the accumulation of N-acyl-l-homoserine lactone (AHL) remains unknown in sphingomonads. In this study, we identified an rsh_US6–1 gene by sequence analysis in Novosphingobium pentaromativorans US6-1, a member of the sphingomonads. RNA-seq was used to determine transcription profiles of the wild type and the ppGpp-deficient rsh_US6–1 deletion mutant (∆rsh). There were 1540 genes in the Rsh_US6–1 regulon, including those involved in common traits of sphingomonads such as exopolysaccharide biosynthesis. Furthermore, both RNA-seq and quantitative real-time polymerase chain reaction (qRT-PCR) showed essential genes for AHL production (novI and novR) were positively regulated by Rsh_US6–1 during the exponential growth phase. A degradation experiment indicated the reason for the AHL absence in ∆rsh was unrelated to the AHL degradation. According to RNA-seq, we proposed σ^E, DksA, Lon protease and RNA degradation enzymes might be involved in the Rsh_US6–1-dependent expression of novI and novR. Here, we report the first transcriptome-wide analysis of the Rsh regulon in sphingomonads and investigate the potential mechanisms regulating AHL accumulation, which is an important step towards understanding the regulatory system of stringent response in sphingomonads. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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22 pages, 3708 KiB

Open AccessArticle

Preliminary RNA-Seq Analysis of Long Non-Coding RNAs Expressed in Human Term Placenta

by Marta Majewska, Aleksandra Lipka, Lukasz Paukszto, Jan Pawel Jastrzebski, Marek Gowkielewicz, Marcin Jozwik and Mariusz Krzysztof Majewski

Int. J. Mol. Sci. 2018, 19(7), 1894; https://doi.org/10.3390/ijms19071894 - 27 Jun 2018

Cited by 22 | Viewed by 4749

Abstract

Development of particular structures and proper functioning of the placenta are under the influence of sophisticated pathways, controlled by the expression of substantial genes that are additionally regulated by long non-coding RNAs (lncRNAs). To date, the expression profile of lncRNA in human term [...] Read more.

Development of particular structures and proper functioning of the placenta are under the influence of sophisticated pathways, controlled by the expression of substantial genes that are additionally regulated by long non-coding RNAs (lncRNAs). To date, the expression profile of lncRNA in human term placenta has not been fully established. This study was conducted to characterize the lncRNA expression profile in human term placenta and to verify whether there are differences in the transcriptomic profile between the sex of the fetus and pregnancy multiplicity. RNA-Seq data were used to profile, quantify, and classify lncRNAs in human term placenta. The applied methodology enabled detection of the expression of 4463 isoforms from 2899 annotated lncRNA loci, plus 990 putative lncRNA transcripts from 607 intergenic regions. Those placentally expressed lncRNAs displayed features such as shorter transcript length, longer exon length, fewer exons, and lower expression levels compared to messenger RNAs (mRNAs). Among all placental transcripts, 175,268 were classified as mRNAs and 15,819 as lncRNAs, and 56,727 variants were discovered within unannotated regions. Five differentially expressed lncRNAs (HAND2-AS1, XIST, RP1-97J1.2, AC010084.1, TTTY15) were identified by a sex-bias comparison. Splicing events were detected within 37 genes and 4 lncRNA loci. Functional analysis of cis-related potential targets for lncRNAs identified 2021 enriched genes. It is presumed that the obtained data will expand the current knowledge of lncRNAs in placenta and human non-coding catalogs, making them more contemporary and specific. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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13 pages, 3005 KiB

Open AccessArticle

miR-25-3p, Positively Regulated by Transcription Factor AP-2α, Regulates the Metabolism of C2C12 Cells by Targeting Akt1

by Feng Zhang, Kun Chen, Hu Tao, Tingting Kang, Qi Xiong, Qianhui Zeng, Yang Liu, Siwen Jiang and Mingxin Chen

Int. J. Mol. Sci. 2018, 19(3), 773; https://doi.org/10.3390/ijms19030773 - 8 Mar 2018

Cited by 15 | Viewed by 4560

Abstract

miR-25, a member of the miR-106b-25 cluster, has been reported as playing an important role in many biological processes by numerous studies, while the role of miR-25 in metabolism and its transcriptional regulation mechanism remain unclear. In this study, gain-of-function and loss-of-function assays [...] Read more.

miR-25, a member of the miR-106b-25 cluster, has been reported as playing an important role in many biological processes by numerous studies, while the role of miR-25 in metabolism and its transcriptional regulation mechanism remain unclear. In this study, gain-of-function and loss-of-function assays demonstrated that miR-25-3p positively regulated the metabolism of C2C12 cells by attenuating phosphoinositide 3-kinase (PI3K) gene expression and triglyceride (TG) content, and enhancing the content of adenosine triphosphate (ATP) and reactive oxygen species (ROS). Furthermore, the results from bioinformatics analysis, dual luciferase assay, site-directed mutagenesis, qRT-PCR, and Western blotting demonstrated that miR-25-3p directly targeted the AKT serine/threonine kinase 1 (Akt1) 3′ untranslated region (3′UTR). The core promoter of miR-25-3p was identified, and the transcription factor activator protein-2α (AP-2α) significantly increased the expression of mature miR-25-3p by binding to its core promoter in vivo, as indicated by the chromatin immunoprecipitation (ChIP) assay, and AP-2α binding also downregulated the expression of Akt1. Taken together, our findings suggest that miR-25-3p, positively regulated by the transcription factor AP-2α, enhances C2C12 cell metabolism by targeting the Akt1 gene. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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13 pages, 3192 KiB

Open AccessArticle

Transcriptomics Evidence for Common Pathways in Human Major Depressive Disorder and Glioblastoma

by Yongfang Xie, Ling Wang, Zengyan Xie, Chuisheng Zeng and Kunxian Shu

Int. J. Mol. Sci. 2018, 19(1), 234; https://doi.org/10.3390/ijms19010234 - 12 Jan 2018

Cited by 13 | Viewed by 4335

Abstract

Depression as a common complication of brain tumors. Is there a possible common pathogenesis for depression and glioma? The most serious major depressive disorder (MDD) and glioblastoma (GBM) in both diseases are studied, to explore the common pathogenesis between the two diseases. In [...] Read more.

Depression as a common complication of brain tumors. Is there a possible common pathogenesis for depression and glioma? The most serious major depressive disorder (MDD) and glioblastoma (GBM) in both diseases are studied, to explore the common pathogenesis between the two diseases. In this article, we first rely on transcriptome data to obtain reliable and useful differentially expressed genes (DEGs) by differential expression analysis. Then, we used the transcriptomics of DEGs to find out and analyze the common pathway of MDD and GBM from three directions. Finally, we determine the important biological pathways that are common to MDD and GBM by statistical knowledge. Our findings provide the first direct transcriptomic evidence that common pathway in two diseases for the common pathogenesis of the human MDD and GBM. Our results provide a new reference methods and values for the study of the pathogenesis of depression and glioblastoma. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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Review

Jump to: Editorial, Research

13 pages, 1407 KiB

Open AccessReview

Adiponectin as Link Factor between Adipose Tissue and Cancer

by Erika Di Zazzo, Rita Polito, Silvia Bartollino, Ersilia Nigro, Carola Porcile, Andrea Bianco, Aurora Daniele and Bruno Moncharmont

Int. J. Mol. Sci. 2019, 20(4), 839; https://doi.org/10.3390/ijms20040839 - 15 Feb 2019

Cited by 101 | Viewed by 7170

Abstract

Adipose tissue is a key regulator of energy balance playing an active role in lipid storage as well as in synthesizing several hormones directly involved in the pathogenesis of obesity. Obesity represents a peculiar risk factor for a growing list of cancers and [...] Read more.

Adipose tissue is a key regulator of energy balance playing an active role in lipid storage as well as in synthesizing several hormones directly involved in the pathogenesis of obesity. Obesity represents a peculiar risk factor for a growing list of cancers and is frequently associated to poor clinical outcome. The mechanism linking obesity and cancer is not completely understood, but, amongst the major players, there are both chronic low-grade inflammation and deregulation of adipokines secretion. In obesity, the adipose tissue is pervaded by an abnormal number of immune cells that create an inflammatory environment supporting tumor cell proliferation and invasion. Adiponectin (APN), the most abundant adipokine, shows anti-inflammatory, anti-proliferative and pro-apoptotic properties. Circulating levels of APN are drastically decreased in obesity, suggesting that APN may represent the link factor between obesity and cancer risk. The present review describes the recent advances on the involvement of APN and its receptors in the etiology of different types of cancer. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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17 pages, 616 KiB

Open AccessReview

Long Non-Coding RNA and Acute Leukemia

by Gabriela Marisol Cruz-Miranda, Alfredo Hidalgo-Miranda, Diego Alberto Bárcenas-López, Juan Carlos Núñez-Enríquez, Julian Ramírez-Bello, Juan Manuel Mejía-Aranguré and Silvia Jiménez-Morales

Int. J. Mol. Sci. 2019, 20(3), 735; https://doi.org/10.3390/ijms20030735 - 9 Feb 2019

Cited by 52 | Viewed by 6453

Abstract

Acute leukemia (AL) is the main type of cancer in children worldwide. Mortality by this disease is high in developing countries and its etiology remains unanswered. Evidences showing the role of the long non-coding RNAs (lncRNAs) in the pathophysiology of hematological malignancies have [...] Read more.

Acute leukemia (AL) is the main type of cancer in children worldwide. Mortality by this disease is high in developing countries and its etiology remains unanswered. Evidences showing the role of the long non-coding RNAs (lncRNAs) in the pathophysiology of hematological malignancies have increased drastically in the last decade. In addition to the contribution of these lncRNAs in leukemogenesis, recent studies have suggested that lncRNAs could be used as biomarkers in the diagnosis, prognosis, and therapeutic response in leukemia patients. The focus of this review is to describe the functional classification, biogenesis, and the role of lncRNAs in leukemogenesis, to summarize the evidence about the lncRNAs which are playing a role in AL, and how these genes could be useful as potential therapeutic targets. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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20 pages, 892 KiB

Open AccessReview

Molecular Mechanisms Underlying the Link between Diet and DNA Methylation

by Fatma Zehra Kadayifci, Shasha Zheng and Yuan-Xiang Pan

Int. J. Mol. Sci. 2018, 19(12), 4055; https://doi.org/10.3390/ijms19124055 - 14 Dec 2018

Cited by 89 | Viewed by 10670

Abstract

DNA methylation is a vital modification process in the control of genetic information, which contributes to the epigenetics by regulating gene expression without changing the DNA sequence. Abnormal DNA methylation—both hypomethylation and hypermethylation—has been associated with improper gene expression, leading to several disorders. [...] Read more.

DNA methylation is a vital modification process in the control of genetic information, which contributes to the epigenetics by regulating gene expression without changing the DNA sequence. Abnormal DNA methylation—both hypomethylation and hypermethylation—has been associated with improper gene expression, leading to several disorders. Two types of risk factors can alter the epigenetic regulation of methylation pathways: genetic factors and modifiable factors. Nutrition is one of the strongest modifiable factors, which plays a direct role in DNA methylation pathways. Large numbers of studies have investigated the effects of nutrition on DNA methylation pathways, but relatively few have focused on the biochemical mechanisms. Understanding the biological mechanisms is essential for clarifying how nutrients function in epigenetics. It is believed that nutrition affects the epigenetic regulations of DNA methylation in several possible epigenetic pathways: mainly, by altering the substrates and cofactors that are necessary for proper DNA methylation; additionally, by changing the activity of enzymes regulating the one-carbon cycle; and, lastly, through there being an epigenetic role in several possible mechanisms related to DNA demethylation activity. The aim of this article is to review the potential underlying biochemical mechanisms that are related to diet modifications in DNA methylation and demethylation. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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33 pages, 1933 KiB

Open AccessReview

Insect Transcription Factors: A Landscape of Their Structures and Biological Functions in Drosophila and beyond

by Zhaojiang Guo, Jianying Qin, Xiaomao Zhou and Youjun Zhang

Int. J. Mol. Sci. 2018, 19(11), 3691; https://doi.org/10.3390/ijms19113691 - 21 Nov 2018

Cited by 41 | Viewed by 9633

Abstract

Transcription factors (TFs) play essential roles in the transcriptional regulation of functional genes, and are involved in diverse physiological processes in living organisms. The fruit fly Drosophila melanogaster, a simple and easily manipulated organismal model, has been extensively applied to study the [...] Read more.

Transcription factors (TFs) play essential roles in the transcriptional regulation of functional genes, and are involved in diverse physiological processes in living organisms. The fruit fly Drosophila melanogaster, a simple and easily manipulated organismal model, has been extensively applied to study the biological functions of TFs and their related transcriptional regulation mechanisms. It is noteworthy that with the development of genetic tools such as CRISPR/Cas9 and the next-generation genome sequencing techniques in recent years, identification and dissection the complex genetic regulatory networks of TFs have also made great progress in other insects beyond Drosophila. However, unfortunately, there is no comprehensive review that systematically summarizes the structures and biological functions of TFs in both model and non-model insects. Here, we spend extensive effort in collecting vast related studies, and attempt to provide an impartial overview of the progress of the structure and biological functions of current documented TFs in insects, as well as the classical and emerging research methods for studying their regulatory functions. Consequently, considering the importance of versatile TFs in orchestrating diverse insect physiological processes, this review will assist a growing number of entomologists to interrogate this understudied field, and to propel the progress of their contributions to pest control and even human health. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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19 pages, 2323 KiB

Open AccessReview

Roles of Tristetraprolin in Tumorigenesis

by Jeong-Min Park, Tae-Hee Lee and Tae-Hong Kang

Int. J. Mol. Sci. 2018, 19(11), 3384; https://doi.org/10.3390/ijms19113384 - 29 Oct 2018

Cited by 42 | Viewed by 7587

Abstract

Genetic loss or mutations in tumor suppressor genes promote tumorigenesis. The prospective tumor suppressor tristetraprolin (TTP) has been shown to negatively regulate tumorigenesis through destabilizing the messenger RNAs of critical genes implicated in both tumor onset and tumor progression. Regulation of TTP has [...] Read more.

Genetic loss or mutations in tumor suppressor genes promote tumorigenesis. The prospective tumor suppressor tristetraprolin (TTP) has been shown to negatively regulate tumorigenesis through destabilizing the messenger RNAs of critical genes implicated in both tumor onset and tumor progression. Regulation of TTP has therefore emerged as an important issue in tumorigenesis. Similar to other tumor suppressors, TTP expression is frequently downregualted in various human cancers, and its low expression is correlated with poor prognosis. Additionally, disruption in the regulation of TTP by various mechanisms results in the inactivation of TTP protein or altered TTP expression. A recent study showing alleviation of Myc-driven lymphomagenesis by the forced expression of TTP has shed light on new therapeutic avenues for cancer prevention and treatment through the restoration of TTP expression. In this review, we summarize key oncogenes subjected to the TTP-mediated mRNA degradation, and discuss how dysregulation of TTP can contribute to tumorigenesis. In addition, the control mechanism underlying TTP expression at the posttranscriptional and posttranslational levels will be discussed. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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16 pages, 265 KiB

Open AccessReview

Selenium-Related Transcriptional Regulation of Gene Expression

by Mikko J. Lammi and Chengjuan Qu

Int. J. Mol. Sci. 2018, 19(9), 2665; https://doi.org/10.3390/ijms19092665 - 8 Sep 2018

Cited by 35 | Viewed by 6101

Abstract

The selenium content of the body is known to control the expression levels of numerous genes, both so-called selenoproteins and non-selenoproteins. Selenium is a trace element essential to human health, and its deficiency is related to, for instance, cardiovascular and myodegenerative diseases, infertility [...] Read more.

The selenium content of the body is known to control the expression levels of numerous genes, both so-called selenoproteins and non-selenoproteins. Selenium is a trace element essential to human health, and its deficiency is related to, for instance, cardiovascular and myodegenerative diseases, infertility and osteochondropathy called Kashin–Beck disease. It is incorporated as selenocysteine to the selenoproteins, which protect against reactive oxygen and nitrogen species. They also participate in the activation of the thyroid hormone, and play a role in immune system functioning. The synthesis and incorporation of selenocysteine occurs via a special mechanism, which differs from the one used for standard amino acids. The codon for selenocysteine is a regular in-frame stop codon, which can be passed by a specific complex machinery participating in translation elongation and termination. This includes a presence of selenocysteine insertion sequence (SECIS) in the 3′-untranslated part of the selenoprotein mRNAs. Nonsense-mediated decay is involved in the regulation of the selenoprotein mRNA levels, but other mechanisms are also possible. Recent transcriptional analyses of messenger RNAs, microRNAs and long non-coding RNAs combined with proteomic data of samples from Keshan and Kashin–Beck disease patients have identified new possible cellular pathways related to transcriptional regulation by selenium. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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24 pages, 7350 KiB

Open AccessReview

Genetic and Epigenetic Control of CDKN1C Expression: Importance in Cell Commitment and Differentiation, Tissue Homeostasis and Human Diseases

by Emanuela Stampone, Ilaria Caldarelli, Alberto Zullo, Debora Bencivenga, Francesco Paolo Mancini, Fulvio Della Ragione and Adriana Borriello

Int. J. Mol. Sci. 2018, 19(4), 1055; https://doi.org/10.3390/ijms19041055 - 2 Apr 2018

Cited by 50 | Viewed by 8805

Abstract

The CDKN1C gene encodes the p57^Kip2 protein which has been identified as the third member of the CIP/Kip family, also including p27^Kip1 and p21^Cip1. In analogy with these proteins, p57^Kip2 is able to bind tightly and inhibit cyclin/cyclin-dependent [...] Read more.

The CDKN1C gene encodes the p57^Kip2 protein which has been identified as the third member of the CIP/Kip family, also including p27^Kip1 and p21^Cip1. In analogy with these proteins, p57^Kip2 is able to bind tightly and inhibit cyclin/cyclin-dependent kinase complexes and, in turn, modulate cell division cycle progression. For a long time, the main function of p57^Kip2 has been associated only to correct embryogenesis, since CDKN1C-ablated mice are not vital. Accordingly, it has been demonstrated that CDKN1C alterations cause three human hereditary syndromes, characterized by altered growth rate. Subsequently, the p57^Kip2 role in several cell phenotypes has been clearly assessed as well as its down-regulation in human cancers. CDKN1C lies in a genetic locus, 11p15.5, characterized by a remarkable regional imprinting that results in the transcription of only the maternal allele. The control of CDKN1C transcription is also linked to additional mechanisms, including DNA methylation and specific histone methylation/acetylation. Finally, long non-coding RNAs and miRNAs appear to play important roles in controlling p57^Kip2 levels. This review mostly represents an appraisal of the available data regarding the control of CDKN1C gene expression. In addition, the structure and function of p57^Kip2 protein are briefly described and correlated to human physiology and diseases. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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