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1.
Plant Cell Environ ; 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39169844

ABSTRACT

Wood serves crucial functions in plants, yet our understanding of the mechanisms governing the composition, arrangement, and dimensions of its cells remains limited. The abrupt transition from nonlianescent to lianescent xylem in lianas represents an excellent model to address the underlying mechanisms, although consistent triggering factors for this process remain uncertain. In this study we examined how physical support attachment impacts the development of lianescent xylem in Bignonia magnifica (Bignoniaceae), employing a comprehensive approach integrating detailed anatomical analysis with gene expression profiling of cambium and differentiating xylem. Our findings demonstrate that attachment to physical supports triggers the formation of lianescent xylem, leading to increased vessel size, broader vessel distribution, reduced fibre content, and higher potential specific water conductivity than nonlianescent xylem. These shifts in wood anatomy coincide with the downregulation of genes associated with cell division and cell wall biosynthesis, and the upregulation of transcription factors, defense/cell death, and hormone-responsive genes in the lianescent xylem. Our findings provide insights into the regulation of xylem differentiation, driven by response to environmental stimuli. Additionally, they shed light on the mechanisms underlying the adaptation of lianas to climbing.

2.
Int J Mol Sci ; 25(8)2024 Apr 14.
Article in English | MEDLINE | ID: mdl-38673927

ABSTRACT

Domestic cat blastocysts cultured without the zona pellucida exhibit reduced implantation capacity. However, the protein expression profile has not been evaluated in these embryos. The objective of this study was to evaluate the protein expression profile of domestic cat blastocysts cultured without the zona pellucida. Two experimental groups were generated: (1) domestic cat embryos generated by IVF and cultured in vitro (zona intact, (ZI)) and (2) domestic cat embryos cultured in vitro without the zona pellucida (zona-free (ZF group)). The cleavage, morula, and blastocyst rates were estimated at days 2, 5 and 7, respectively. Day 7 blastocysts and their culture media were subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS). The UniProt Felis catus database was used to identify the standard proteome. No significant differences were found in the cleavage, morula, or blastocyst rates between the ZI and ZF groups (p > 0.05). Proteomic analysis revealed 22 upregulated and 20 downregulated proteins in the ZF blastocysts. Furthermore, 14 proteins involved in embryo development and implantation were present exclusively in the culture medium of the ZI blastocysts. In conclusion, embryo culture without the zona pellucida did not affect in vitro development, but altered the protein expression profile and release of domestic cat blastocysts.


Subject(s)
Blastocyst , Proteomics , Zona Pellucida , Animals , Blastocyst/metabolism , Zona Pellucida/metabolism , Cats , Proteomics/methods , Embryo Culture Techniques , Secretome/metabolism , Female , Fertilization in Vitro , Proteome/metabolism , Embryonic Development , Tandem Mass Spectrometry , Chromatography, Liquid
3.
Rev. Assoc. Med. Bras. (1992, Impr.) ; Rev. Assoc. Med. Bras. (1992, Impr.);70(8): e20240263, 2024. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1569463

ABSTRACT

SUMMARY OBJECTIVE: The aim of the study was to examine the expression profile of genes (APOE, FTO, and LPL) associated with metabolic syndrome (MetS) in subjects with concomitant atrial fibrillation (AF). METHODS: A total of 690 subjects were categorized into control, AF without MetS, and AF with MetS. RESULTS: The expression profiles of the APOE, FTO, and LPL genes were decreased in AF subjects and AF subjects with MetS as compared to the controls. In AF without the MetS group, an inverse relationship was found between the expression of the LPL gene with body mass index (BMI) and a positive relationship with creatine kinase-MB, whereas expression of the FTO gene was inversely associated with fasting blood glucose and positively with cardiac troponin I in AF suffering from MetS. Expression of the LPL gene was directly linked with systolic blood pressure (SBP) and high-density lipoprotein-cholesterol (HDL-C), whereas an inverse correlation with heart rate and expression of the FTO gene in AF with MetS were shown. The expression of the LPL gene was inversely related to BMI in subjects with AF. The expression of the LPL gene was positively correlated with SBP and HDL-C and negatively correlated with heart rate, while the expression of the FTO gene was an important predictor of AF with MetS. CONCLUSION: The decreased expression of APOE, FTO, and LPL genes in AF with and without MetS indicates their potential contributing role in the pathogenesis of AF.

4.
Biomedicines ; 11(10)2023 Oct 11.
Article in English | MEDLINE | ID: mdl-37893128

ABSTRACT

(1) Background: Sepsis is present in nearly 90% of critically ill patients with community-acquired pneumonia (CAP). This systematic review updates the information on studies that have assessed gene expression profiles in critically ill septic patients with CAP. (2) Methods: We searched for studies that satisfied the following criteria: (a) expression profile in critically ill patients with sepsis due to CAP, (b) presence of a control group, and (c) adult patients. Over-representation analysis was performed with clusterProfiler using the Hallmark and Reactome collections. (3) Results: A total of 4312 differentially expressed genes (DEGs) and sRNAs were included in the enrichment analysis. In the Hallmark collection, genes regulated by nuclear factor kappa B in response to tumor necrosis factor, genes upregulated by signal transducer and activator of transcription 5 in response to interleukin 2 stimulation, genes upregulated in response to interferon-gamma, genes defining the inflammatory response, a subgroup of genes regulated by MYC-version 1 (v1), and genes upregulated during transplant rejection were significantly enriched in critically ill septic patients with CAP. Moreover, 88 pathways were identified in the Reactome database. (4) Conclusions: This study summarizes the reported DEGs in critically ill septic patients with CAP and investigates their functional implications. The results highlight the complexity of immune responses during CAP.

5.
Ann Hepatol ; 28(5): 101124, 2023.
Article in English | MEDLINE | ID: mdl-37286166

ABSTRACT

INTRODUCTION AND OBJECTIVES: The development of hepatocellular carcinoma (HCC) is a multi-step process that accumulates genetic and epigenetic alterations, including changes in circular RNA (circRNA). This study aimed to understand the alterations in circRNA expression in HCC development and metastasis and to explore the biological functions of circRNA. MATERIALS AND METHODS: Ten pairs of adjacent chronic hepatitis tissues and HCC tissues from patients without venous metastases, and ten HCC tissues from patients with venous metastases were analyzed using human circRNA microarrays. Differentially expressed circRNAs were then validated by quantitative real-time PCR. In vitro and in vivo assays were performed to assess the roles of the circRNA in HCC progression. RNA pull-down assay, mass spectrometry analysis, and RNA-binding protein immunoprecipitation were conducted to explore the protein partners of the circRNA. RESULTS: CircRNA microarrays revealed that the expression patterns of circRNAs across the three groups were significantly different. Among these, hsa_circ_0098181 was validated to be lowly expressed and associated with poor prognosis in HCC patients. Ectopic expression of hsa_circ_0098181 delayed HCC metastasis in vitro and in vivo. Mechanistically, hsa_circ_0098181 sequestered eukaryotic translation elongation factor 2 (eEF2) and dissociated eEF2 from filamentous actin (F-actin) to prevent F-actin formation, which blocked activation of the Hippo signaling pathway. In addition, the RNA binding protein Quaking-5 bound directly to hsa_circ_0098181 and induced its biogenesis. CONCLUSIONS: Our study reveals changes in circRNA expression from chronic hepatitis, primary HCC, to metastatic HCC. Further, the QKI5-hsa_circ_0098181-eEF2-Hippo signaling pathway exerts a regulatory role in HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , Humans , Carcinoma, Hepatocellular/pathology , RNA, Circular/genetics , Liver Neoplasms/pathology , Peptide Elongation Factor 2/genetics , Peptide Elongation Factor 2/metabolism , Hippo Signaling Pathway , Actins/metabolism , Hepatitis, Chronic , MicroRNAs/genetics , Gene Expression Regulation, Neoplastic
6.
Biometals ; 36(5): 1081-1108, 2023 10.
Article in English | MEDLINE | ID: mdl-37209221

ABSTRACT

Bacillus toyonensis SFC 500-1E is a member of the consortium SFC 500-1 able to remove Cr(VI) and simultaneously tolerate high phenol concentrations. In order to elucidate mechanisms utilized by this strain during the bioremediation process, the differential expression pattern of proteins was analyzed when it grew with or without Cr(VI) (10 mg/L) and Cr(VI) + phenol (10 and 300 mg/L), through two complementary proteomic approaches: gel-based (Gel-LC) and gel-free (shotgun) nanoUHPLC-ESI-MS/MS. A total of 400 differentially expressed proteins were identified, out of which 152 proteins were down-regulated under Cr(VI) and 205 up-regulated in the presence of Cr(VI) + phenol, suggesting the extra effort made by the strain to adapt itself and keep growing when phenol was also added. The major metabolic pathways affected include carbohydrate and energetic metabolism, followed by lipid and amino acid metabolism. Particularly interesting were also ABC transporters and the iron-siderophore transporter as well as transcriptional regulators that can bind metals. Stress-associated global response involving the expression of thioredoxins, SOS response, and chaperones appears to be crucial for the survival of this strain under treatment with both contaminants. This research not only provided a deeper understanding of B. toyonensis SFC 500-1E metabolic role in Cr(VI) and phenol bioremediation process but also allowed us to complete an overview of the consortium SFC 500-1 behavior. This may contribute to an improvement in its use as a bioremediation strategy and also provides a baseline for further research.


Subject(s)
Phenol , Proteomics , Biodegradation, Environmental , Chromium/chemistry , Phenol/chemistry , Phenol/metabolism , Phenols , Tandem Mass Spectrometry
7.
Plants (Basel) ; 12(5)2023 Mar 03.
Article in English | MEDLINE | ID: mdl-36904008

ABSTRACT

Gene co-expression networks are powerful tools to understand functional interactions between genes. However, large co-expression networks are difficult to interpret and do not guarantee that the relations found will be true for different genotypes. Statistically verified time expression profiles give information about significant changes in expressions through time, and genes with highly correlated time expression profiles, which are annotated in the same biological process, are likely to be functionally connected. A method to obtain robust networks of functionally related genes will be useful to understand the complexity of the transcriptome, leading to biologically relevant insights. We present an algorithm to construct gene functional networks for genes annotated in a given biological process or other aspects of interest. We assume that there are genome-wide time expression profiles for a set of representative genotypes of the species of interest. The method is based on the correlation of time expression profiles, bound by a set of thresholds that assure both, a given false discovery rate, and the discard of correlation outliers. The novelty of the method consists in that a gene expression relation must be repeatedly found in a given set of independent genotypes to be considered valid. This automatically discards relations particular to specific genotypes, assuring a network robustness, which can be set a priori. Additionally, we present an algorithm to find transcription factors candidates for regulating hub genes within a network. The algorithms are demonstrated with data from a large experiment studying gene expression during the development of the fruit in a diverse set of chili pepper genotypes. The algorithm is implemented and demonstrated in a new version of the publicly available R package "Salsa" (version 1.0).

8.
Biomedicines ; 11(2)2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36830965

ABSTRACT

(1) Background: Information regarding gene expression profiles and the prognosis of community-acquired pneumonia (CAP) is scarce. We aimed to examine the differences in the gene expression profiles in peripheral blood at hospital admission between patients with CAP who died during hospitalization and those who survived. (2) Methods: This is a multicenter study of nonimmunosuppressed adult patients who required hospitalization for CAP. Whole blood samples were obtained within 24 h of admission for genome-expression-profile analysis. Gene expression profiling identified both differentially expressed genes and enriched gene sets. (3) Results: A total of 198 samples from adult patients who required hospitalization for CAP were processed, of which 13 were from patients who died. Comparison of gene expression between patients who died and those who survived yielded 49 differentially expressed genes, 36 of which were upregulated and 13 downregulated. Gene set enrichment analysis (GSEA) identified four positively enriched gene sets in survivors, mainly associated with the interferon-alpha response, apoptosis, and sex hormone pathways. Similarly, GSEA identified seven positively enriched gene sets, associated with the oxidative stress, endoplasmic reticulum stress, oxidative phosphorylation, and angiogenesis pathways, in the patients who died. Protein-protein-interaction-network analysis identified FOS, CDC42, SLC26A10, EIF4G2, CCND3, ASXL1, UBE2S, and AURKA as the main gene hubs. (4) Conclusions: We found differences in gene expression profiles at hospital admission between CAP patients who died and those who survived. Our findings may help to identify novel candidate pathways and targets for potential intervention and biomarkers for risk stratification.

9.
Rev. bras. zootec ; 52: e20210149, 2023. tab, graf
Article in English | VETINDEX | ID: biblio-1436790

ABSTRACT

To characterize the N6-methyladenosine (m6A)-related gene expression profiles in various tissues of Meishan pigs at different stages, m6A modification-related genes (METTL3, METTL14, METTL16, WTAP, RBM15, and FTO) were detected from newborn to physical maturity of Meishan pigs at eight important developmental stages (1, 7, 14, 21, 28, 35, 134, and 158 days old). The expression of m6A-related genes was tissue-specific. Furthermore, the level of METTL3 messenger RNA (mRNA) was higher on day 35 than in other stages in most tissues, and the expression of METTL14 increased after day 35, and FTO exhibited a peak on day 14 in muscle, intestine, lymph nodes, thymus, and kidney. This study provided a reference for an in-depth study of the expression patterns of m6A modification-related genes in Meishan pigs.


Subject(s)
Animals , Swine/genetics , Genes , Life Cycle Stages
10.
Int J Mol Sci ; 23(19)2022 Sep 29.
Article in English | MEDLINE | ID: mdl-36232817

ABSTRACT

Given the importance of menstrual blood in the pathogenesis of endometriosis and the multifunctional roles of menstrual mesenchymal stem cells (MenSCs) in regenerative medicine, this issue has gained prominence in the scientific community. Moreover, recent reviews highlight how robust the integrated assessment of omics data are for endometriosis. To our knowledge, no study has applied the multi-omics approaches to endometriosis MenSCs. This is a case-control study at a university-affiliated hospital. MenSCs transcriptome and proteome data were obtained by RNA-seq and UHPLC-MS/MS detection. Among the differentially expressed proteins and genes, we emphasize ATF3, ID1, ID3, FOSB, SNAI1, NR4A1, EGR1, LAMC3, and ZFP36 genes and MT2A, TYMP, COL1A1, COL6A2, and NID2 proteins that were already reported in the endometriosis. Our functional enrichment analysis reveals integrated modulating signaling pathways such as epithelial-mesenchymal transition (↑) and PI3K signaling via AKT to mTORC1 (↓ in proteome), mTORC1 signaling, TGF beta signaling, TNFA signaling via NFkB, IL6 STAT3 signaling, and response to hypoxia via HIF1A targets (↑ in transcriptome). Our findings highlight primary changes in the endometriosis MenSCs, suggesting that the chronic inflammatory endometrial microenvironment can modulate these cells, providing opportunities for endometriosis etiopathogenesis. Moreover, they identify challenges for future research leveraging knowledge for regenerative and precision medicine in endometriosis.


Subject(s)
Endometriosis , Mesenchymal Stem Cells , Case-Control Studies , Cell Proliferation , Endometriosis/pathology , Female , Humans , Interleukin-6 , Laminin , Mechanistic Target of Rapamycin Complex 1/metabolism , Menstruation , Mesenchymal Stem Cells/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proteome , Proto-Oncogene Proteins c-akt/metabolism , Tandem Mass Spectrometry , Transcriptome , Transforming Growth Factor beta/genetics
11.
Genes Chromosomes Cancer ; 61(7): 437-442, 2022 07.
Article in English | MEDLINE | ID: mdl-35253299

ABSTRACT

CRLF2 overexpression has been described as a biomarker of poor prognosis in T-cell acute lymphoblastic leukemia (T-ALL). In the present study, we aimed to unravel the genomic profile underlying CRLF2 overexpression (CRLF2-high) by analyzing RNA-seq, WES, and SNP-array data from 264 T-ALL patients and five cell lines deposited on the TARGET initiative, Cancer Cell Line Encyclopedia and Gene Expression Omnibus. These data allowed us to delineate the genomic landscape of CRLF2-high in T-ALL, which was associated with PTEN, JAK3, PHF6, EZH2, and RUNX1 mutations. We also observed an enrichment of CRLF2-high in early T-precursor (ETP)-ALL (23.08% vs. 4.02%, P = 7.579e-06 ) and a very similar gene upregulation profile between these two entities. The inhibition of BET (iBET) proteins is a strategy previously demonstrated to reverse the gene upregulation pattern of ETP cells through restoration of polycomb repressive complex 2 (PRC2) activity. While CRLF2 expression was rescued by using this strategy in LOUCY (untreated vs. iBET P = 0.0095, DMSO vs. iBET P = 0.0286), a classical ETP-ALL cell line, PRC2 loss was not sufficient to promote CRLF2 upregulation in JURKAT, a more mature T-ALL cell line. Considering the role of IKZF1 in CRLF2 regulation and in recruitment of PCR2, we evaluated IKZF1 status according to CRLF2-expression subgroups. We identified that IKZF1 transcripts with intron retention were upregulated in the CRLF2-high subgroup. Here, we delineated the gene expression profile of CRLF2-high T-ALL samples and unraveled the crucial role of PRC2 in CRLF2 regulation in ETP-ALL.


Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cells, T-Lymphoid , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Humans , Ikaros Transcription Factor/genetics , Ikaros Transcription Factor/metabolism , Polycomb Repressive Complex 2 , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cells, T-Lymphoid/metabolism , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Receptors, Cytokine/genetics , Receptors, Cytokine/metabolism
12.
Plants (Basel) ; 10(12)2021 Nov 29.
Article in English | MEDLINE | ID: mdl-34961093

ABSTRACT

Macroautophagy/autophagy is a fundamental catabolic pathway that maintains cellular homeostasis in eukaryotic cells by forming double-membrane-bound vesicles named autophagosomes. The autophagy family genes remain largely unexplored except in some model organisms. Legumes are a large family of economically important crops, and knowledge of their important cellular processes is essential. Here, to first address the knowledge gaps, we identified 17 ATG families in Phaseolus vulgaris, Medicago truncatula and Glycine max based on Arabidopsis sequences and elucidated their phylogenetic relationships. Second, we dissected ATG18 in subfamilies from early plant lineages, chlorophytes to higher plants, legumes, which included a total of 27 photosynthetic organisms. Third, we focused on the ATG18 family in P. vulgaris to understand the protein structure and developed a 3D model for PvATG18b. Our results identified ATG homologs in the chosen legumes and differential expression data revealed the nitrate-responsive nature of ATG genes. A multidimensional scaling analysis of 280 protein sequences from 27 photosynthetic organisms classified ATG18 homologs into three subfamilies that were not based on the BCAS3 domain alone. The domain structure, protein motifs (FRRG) and the stable folding conformation structure of PvATG18b revealing the possible lipid-binding sites and transmembrane helices led us to propose PvATG18b as the functional homolog of AtATG18b. The findings of this study contribute to an in-depth understanding of the autophagy process in legumes and improve our knowledge of ATG18 subfamilies.

13.
Cancers (Basel) ; 13(20)2021 Oct 15.
Article in English | MEDLINE | ID: mdl-34680332

ABSTRACT

Thyroid cancer is the most common endocrine malignancy. However, the cytological diagnosis of follicular thyroid carcinoma (FTC), Hürthle cell carcinoma (HCC), and follicular variant of papillary thyroid carcinoma (FVPTC) and their benign counterparts is a challenge for preoperative diagnosis. Nearly 20-30% of biopsied thyroid nodules are classified as having indeterminate risk of malignancy and incur costs to the health care system. Based on that, 120 patients were screened for the main driver mutations previously described in thyroid cancer. Subsequently, 14 mutation-negative cases that are the main source of diagnostic errors (FTC, HCC, or FVPTC) underwent RNA-Sequencing analysis. Somatic variants in candidate driver genes (ECD, NUP98,LRP1B, NCOR1, ATM, SOS1, and SPOP) and fusions were described. NCOR1 and SPOP variants underwent validation. Moreover, expression profiling of driver-negative samples was compared to 16 BRAF V600E, RAS, or PAX8-PPARg positive samples. Negative samples were separated in two clusters, following the expression pattern of the RAS/PAX8-PPARg or BRAF V600E positive samples. Both negative groups showed distinct BRS, ERK, and TDS scores, tumor mutation burden, signaling pathways and immune cell profile. Altogether, here we report novel gene variants and describe cancer-related pathways that might impact preoperative diagnosis and provide insights into thyroid tumor biology.

14.
Biomedicines ; 9(9)2021 Sep 18.
Article in English | MEDLINE | ID: mdl-34572445

ABSTRACT

Juvenile nasopharyngeal angiofibroma (JNA) is a rare fibrovascular benign tumor showing an invasive growth pattern and affecting mainly male adolescents. We investigated the role of epithelial-mesenchymal transition (EMT) and WNT signaling pathways in JNA. Gene expression profiles using nine JNA paired with four inferior nasal turbinate samples were interrogated using a customized 2.3K microarray platform containing genes mainly involved in EMT and WNT/PI3K pathways. The expression of selected genes (BCL2, CAV1, CD74, COL4A2, FZD7, ING1, LAMB1, and RAC2) and proteins (BCL2, CAV1, CD74, FZD7, RAF1, WNT5A, and WNT5B) was investigated by RT-qPCR (28 cases) and immunohistochemistry (40 cases), respectively. Among 104 differentially expressed genes, we found a significantly increased expression of COL4A2 and LAMB1 and a decreased expression of BCL2 and RAC2 by RT-qPCR. The immunohistochemistry analysis revealed a low expression of BCL2 and a negative to moderate expression of FZD7 in most samples, while increased CAV1 and RAF1 expression were detected. Moderate to strong CD74 protein expression was observed in endothelial and inflammatory cells. A significant number of JNAs (78%) presented reduced WNT5A and increased WNT5B expression. Overall, the transcript and protein profile indicated the involvement of EMT and WNT pathways in JNA. These candidates are promising druggable targets for treating JNA.

15.
Braz J Microbiol ; 52(4): 2439-2446, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34351602

ABSTRACT

Dermatophytes are a group of eukaryotic microorganisms characterized by high capacity to colonize keratinized structures such as the skin, hair, and nails. Over the past years, the incidence of infections caused by zoophilic species, e.g., Trichophyton verrucosum, has been increasing in some parts of the world, especially in Europe. Moreover, the emergence of recalcitrant dermatophytoses and in vitro resistant dermatophytes has become a cause of concern worldwide. Here, we analyzed the mechanisms underlying resistance to fluconazole among clinical isolates of T. verrucosum. Quantitative RT-PCR was carried out to determine the relative expression levels of mRNA transcripts of ERG3, ERG6, and ERG11 genes in the fungal samples using the housekeeping gene GAPDH as a reference. Our results showed that the upregulation of the ERG gene expression is a possible mechanism of resistance to fluconazole in this species. Furthermore, ERG11 is the most statistically significantly overexpressed gene in the pool of fluconazole-resistant T. verrucosum isolates. Additionally, we have demonstrated that exposure to fluconazole increases the levels of expression of ERG genes in fluconazole-resistant isolates of T. verrucosum. In conclusion, this study has shown one of the possible mechanisms of resistance to fluconazole among zoophilic dermatophytes, which involves the maintenance of high levels of expression of ERG genes after drug exposure.


Subject(s)
Arthrodermataceae , Drug Resistance, Fungal , Fluconazole , Fungal Proteins , Transcriptional Regulator ERG/genetics , Animals , Antifungal Agents/pharmacology , Arthrodermataceae/drug effects , Arthrodermataceae/genetics , Drug Resistance, Fungal/genetics , Fluconazole/pharmacology , Fungal Proteins/genetics , Gene Expression Regulation, Fungal , Humans , Trichophyton/drug effects , Trichophyton/genetics
16.
Clin Transl Oncol ; 23(4): 856-865, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32880047

ABSTRACT

BACKGROUND: Deregulated expression of cell cycle regulators p27 and p16 is associated with cancer progression. p27kip1 and p16INKa are a cyclin dependent kinase inhibitor whose major target is the cyclinE/CDK2 and cyclinD/CDK4/6 complex, respectively, that governs cell cycle transition from late G1 to S phase. METHODS: We recruited biopsies of a total of 84 subjects including 72 primary tumor biopsies from histopathologically proven gastric carcinoma, 8 adjacent controls and 12 independent controls. We used gastric cancer cell line, AGS, for validation of our data. Expression profiling at transcript level was done by semi-quantitative RT-PCR and at proteome level by immunohistochemistry and immunofluorescence. Receiver operator characteristics analysis was done for determining the diagnostic utility of p27 and p16 with respect to the sensitivity and specificity. RESULTS: We demonstrate that p27 and p16 are frequently over expressed in early stages of gastric carcinoma. Our semi-quantitative data show a significant upregulation of p27 (Mean ± SEM, 0.4771 ± 0.0895; p = 0.0001) and p16 (Mean ± SEM, 0.4676 ± 0.04305; p = 0.0001) at mRNA level. Concordant to semi-quantitative data, immunohistochemistry data also showed a significant upregulation of p27 (Mean ± SEM, 196.4 ± 10.84; p < 0.0001) and p16 (Mean ± SEM, 100.4 ± 23.71; p < 0.0001) at protein level. CONCLUSIONS: The present study showed that the significant upregulation of p27 and p16 were associated with early events in gastric carcinogenesis. Our data suggests that clinical correlation of these differentially expressed genes may be useful as diagnostic biomarkers for early detection of gastric carcinoma and promising therapeutics target for GC patients.


Subject(s)
Cyclin-Dependent Kinase Inhibitor p16/metabolism , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Stomach Neoplasms/metabolism , Adult , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Disease Progression , Early Detection of Cancer , Female , Fluorescent Antibody Technique , G1 Phase Cell Cycle Checkpoints , Humans , Immunohistochemistry , Male , Middle Aged , RNA, Messenger/metabolism , ROC Curve , Reverse Transcriptase Polymerase Chain Reaction , S Phase Cell Cycle Checkpoints , Sensitivity and Specificity , Stomach Neoplasms/diagnosis , Stomach Neoplasms/pathology , Up-Regulation , Young Adult
17.
Int J Mol Sci ; 21(20)2020 Oct 16.
Article in English | MEDLINE | ID: mdl-33081152

ABSTRACT

Gastric cancer (GC) represents a notable amount of morbidity and mortality worldwide. Understanding the molecular basis of CG will offer insight into its pathogenesis in an attempt to identify new molecular biomarkers to early diagnose this disease. Therefore, studies involving small non-coding RNAs have been widely explored. Among these, PIWI-interacting RNAs (piRNAs) are an emergent class that can play important roles in carcinogenesis. In this study, small-RNA sequencing was used to identify the global piRNAs expression profile (piRNome) of gastric cancer patients. We found 698 piRNAs in gastric tissues, 14 of which were differentially expressed (DE) between gastric cancer (GC), adjacent to gastric cancer (ADJ), and non-cancer tissues (NC). Moreover, three of these DE piRNAs (piR-48966*, piR-49145, piR-31335*) were differently expressed in both GC and ADJ samples in comparison to NC samples, indicating that the tumor-adjacent tissue was molecularly altered and should not be considered as a normal control. These three piRNAs are potential risk biomarkers for GC, especially piR-48966* and piR-31335*. Furthermore, an in-silico search for mRNAs targeted by the differentially expressed piRNAs revealed that these piRNAs may regulate genes that participate in cancer-related pathways, suggesting that these small non-coding RNAs may be directly and indirectly involved in gastric carcinogenesis.


Subject(s)
Biomarkers, Tumor/genetics , RNA, Small Interfering/genetics , Stomach Neoplasms/genetics , Transcriptome , Biomarkers, Tumor/metabolism , Gene Regulatory Networks , Humans , Neoplasm Metastasis , RNA, Small Interfering/metabolism , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology
18.
J Endocr Soc ; 4(11): bvaa136, 2020 Nov 01.
Article in English | MEDLINE | ID: mdl-33123655

ABSTRACT

To study thyroid hormone (TH) signaling in the human brain, we analyzed published microarray data sets of the temporal pole (Brodmann area 38) of 19 deceased donors. An index of TH signaling built on the expression of 19 well known TH-responsive genes in mouse brains (T3S+) varied from 0.92 to 1.1. After Factor analysis, T3S+ correlated independently with the expression of TH transporters (MCT8, LAT2), TH receptor (TR) beta and TR coregulators (CARM1, MED1, KAT2B, SRC2, SRC3, NCOR2a). Unexpectedly, no correlation was found between T3S+ vs DIO2, DIO3, SRC1, or TRα. An unbiased systematic analysis of the entire transcriptome identified a set of 1649 genes (set #1) with strong positive correlation with T3S+ (r > 0.75). Factor analysis of set #1 identified 2 sets of genes that correlated independently with T3S+, sets #2 (329 genes) and #3 (191 genes). When processed through the Molecular Signatures Data Base (MSigDB), both sets #2 and #3 were enriched with Gene Ontology (GO)-sets related to synaptic transmission and metabolic processes. Ranking individual human brain donors according to their T3S+ led us to identify 1262 genes (set #4) with >1.3-fold higher expression in the top half. The analysis of the overlapped genes between sets #1 and #4 resulted in 769 genes (set #5), which have a very similar MSigDB signature as sets #2 and #3. In conclusion, gene expression in the human temporal pole can be assessed through T3S+ and fluctuates with subtle variations in local TH signaling.

19.
Front Cell Dev Biol ; 8: 561, 2020.
Article in English | MEDLINE | ID: mdl-32733882

ABSTRACT

Adipogenesis, osteogenesis and chondrogenesis of human mesenchymal stem/stromal cells (MSC) are complex and highly regulated processes. Over the years, several studies have focused on understanding the mechanisms involved in the MSC commitment to the osteogenic, adipogenic and/or chondrogenic phenotypes. High-throughput methodologies have been used to investigate the gene expression profile during differentiation. Association of data analysis of mRNAs, microRNAs, circular RNAs and long non-coding RNAs, obtained at different time points over these processes, are important to depict the complexity of differentiation. This review will discuss the results that were highlighted in transcriptome analyses of MSC undergoing adipogenic, osteogenic and chondrogenic differentiation. The focus is to shed light on key molecules, main signaling pathways and biological processes related to different time points of adipogenesis, osteogenesis and chondrogenesis.

20.
Cells ; 9(8)2020 07 22.
Article in English | MEDLINE | ID: mdl-32707870

ABSTRACT

Nile tilapia is the third most cultivated fish worldwide and a novel model species for evolutionary studies. Aiming to improve productivity and contribute to the selection of traits of economic impact, biotechnological approaches have been intensively applied to species enhancement. In this sense, recent studies have focused on the multiple roles played by microRNAs (miRNAs) in the post-transcriptional regulation of protein-coding genes involved in the emergence of phenotypes with relevance for aquaculture. However, there is still a growing demand for a reference resource dedicated to integrating Nile Tilapia miRNA information, obtained from both experimental and in silico approaches, and facilitating the analysis and interpretation of RNA sequencing data. Here, we present an open repository dedicated to Nile Tilapia miRNAs: the "miRTil database". The database stores data on 734 mature miRNAs identified in 11 distinct tissues and five key developmental stages. The database provides detailed information about miRNA structure, genomic context, predicted targets, expression profiles, and relative 5p/3p arm usage. Additionally, miRTil also includes a comprehensive pre-computed miRNA-target interaction network containing 4936 targets and 19,580 interactions.


Subject(s)
Cichlids/genetics , Cichlids/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Transcriptome , Animals , Base Sequence , Databases, Genetic , Gene Expression Regulation, Developmental , Gene Regulatory Networks , High-Throughput Nucleotide Sequencing/methods , Humans , Protein Interaction Maps , RNA Processing, Post-Transcriptional , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sequence Analysis, RNA/methods , Zebrafish/genetics , Zebrafish/metabolism
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