scholarly journals Reciprocal Changes in miRNA Expression with Pigmentation and Decreased Proliferation Induced in Mouse B16F1 Melanoma Cells by l-Tyrosine and 5-Bromo-2′-Deoxyuridine

2021 ◽  
Vol 22 (4) ◽  
pp. 1591
Author(s):  
Hernán Mauricio Rivera ◽  
Esther Natalia Muñoz ◽  
Daniel Osuna ◽  
Mauro Florez ◽  
Michael Carvajal ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Expression Profiles ◽  
Cell Cycle Control ◽  
Network Models ◽  
Bioinformatic Analysis ◽  
Melanoma Cells ◽  
Cellular Processes ◽  
And Control ◽  
Molecular Bases ◽  
Small Rnaseq

Background: Many microRNAs have been identified as critical mediators in the progression of melanoma through its regulation of genes involved in different cellular processes such as melanogenesis, cell cycle control, and senescence. However, microRNAs’ concurrent participation in syngeneic mouse B16F1 melanoma cells simultaneously induced decreased proliferation and differential pigmentation by exposure to 5-Brd-2′-dU (5’Bromo-2-deoxyuridine) and L-Tyr (L-Tyrosine) respectively, is poorly understood. Aim: To evaluate changes in the expression of microRNAs and identify which miRNAs in-network may contribute to the functional bases of phenotypes of differential pigmentation and reduction of proliferation in B16F1 melanoma cells exposed to 5-Brd-2′-dU and L-Tyr. Methods: Small RNAseq evaluation of the expression profiles of miRNAs in B16F1 melanoma cells exposed to 5-Brd-2′-dU (2.5 μg/mL) and L-Tyr (5 mM), as well as the expression by qRT-PCR of some molecular targets related to melanogenesis, cell cycle, and senescence. By bioinformatic analysis, we constructed network models of regulation and co-expression of microRNAs. Results: We confirmed that stimulation or repression of melanogenesis with L-Tyr or 5-Brd-2′-dU, respectively, generated changes in melanin concentration, reduction in proliferation, and changes in expression of microRNAs 470-3p, 470-5p, 30d-5p, 129-5p, 148b-3p, 27b-3p, and 211-5p, which presented patterns of coordinated and reciprocal co-expression, related to changes in melanogenesis through their putative targets Mitf, Tyr and Tyrp1, and control of cell cycle and senescence: Cyclin D1, Cdk2, Cdk4, p21, and p27. Conclusions: These findings provide insights into the molecular biology of melanoma of the way miRNAs are coordinated and reciprocal expression that may operate in a network as molecular bases for understanding changes in pigmentation and decreased proliferation induced in B16F1 melanoma cells exposed to L-Tyr and 5-Brd-2′-dU.

scholarly journals Gene Expression Profiles Associated with Radio-Responsiveness in Locally Advanced Rectal Cancer

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 500
Author(s):  
Jeeyong Lee ◽  
Junhye Kwon ◽  
DaYeon Kim ◽  
Misun Park ◽  
KwangSeok Kim ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Expression Profiles ◽  
Cell Cycle Control ◽  
Methylation Status ◽  
Locally Advanced ◽  
Gene Expression Profiles ◽  
Advanced Rectal Cancer ◽  
Bioinformatic Analysis ◽  
Locally Advanced Rectal Cancer ◽  
Genes Encoding

LARC patients were sorted according to their radio-responsiveness and patient-derived organoids were established from the respective cancer tissues. Expression profiles for each group were obtained using RNA-seq. Biological and bioinformatic analysis approaches were used in deciphering genes and pathways that participate in the radio-resistance of LARC. Thirty candidate genes encoding proteins involved in radio-responsiveness–related pathways, including the immune system, DNA repair and cell-cycle control, were identified. Interestingly, one of the candidate genes, cathepsin E (CTSE), exhibited differential methylation at the promoter region that was inversely correlated with the radio-resistance of patient-derived organoids, suggesting that methylation status could contribute to radio-responsiveness. On the basis of these results, we plan to pursue development of a gene chip for diagnosing the radio-responsiveness of LARC patients, with the hope that our efforts will ultimately improve the prognosis of LARC patients.

Gene expression profiling of multiple myeloma reveals molecular portraits in relation to the pathogenesis of the disease

Blood ◽  
2003 ◽  
Vol 101 (12) ◽  
pp. 4998-5006 ◽  
Author(s):  
Florence Magrangeas ◽  
Valéry Nasser ◽  
Hervé Avet-Loiseau ◽  
Béatrice Loriod ◽  
Olivier Decaux ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Multiple Myeloma ◽  
Immune Response ◽  
Light Chain ◽  
Dna Microarrays ◽  
Chromosomal Abnormalities ◽  
Expression Profiles ◽  
Cell Cycle Control ◽  
Primary Tumors

AbstractAlthough multiple myeloma (MM) is a unique entity, a marked heterogeneity is actually observed among the patients, which has been first related to immunoglobulin (Ig) types and light chain subtypes and more recently to chromosomal abnormalities. To further investigate this genetic heterogeneity, we analyzed gene expression profiles of 92 primary tumors according to their Ig types and light chain subtypes with DNA microarrays. Several clusters of genes involved in various biologic functions such as immune response, cell cycle control, signaling, apoptosis, cell adhesion, and structure significantly discriminated IgA- from IgG-MM. Genes associated with inhibition of differentiation and apoptosis induction were up-regulated while genes associated with immune response, cell cycle control, and apoptosis were down-regulated in IgA-MM. According to the expression of the 61 most discriminating genes, BJ-MM represented a separate subgroup that did not express either the genes characteristic of IgG-MM or those of IgA-MM at a high level. This suggests that transcriptional programs associated to the switch could be maintained up to plasma cell differentiation. Several genes whose products are known to stimulate bone remodeling discriminate between κ- and λ-MM. One of these genes, Mip-1α, was overexpressed in the κ subgroup. In addition, we established a strong association (P = .0001) between κ subgroup expressing high levels of Mip-1α and active myeloma bone disease. This study shows that DNA microarrays enable us to perform a molecular dissection of the bioclinical diversity of MM and provide new molecular tools to investigate the pathogenesis of malignant plasma cells.

scholarly journals Evidence for a Structural Relationship between BRCT Domains and the Helicase Domains of the Replication Initiators Encoded by the Polyomaviridae and Papillomaviridae Families of DNA Tumor Viruses

2008 ◽  
Vol 82 (17) ◽  
pp. 8849-8862 ◽  
Author(s):  
Anuradha Kumar ◽  
Woo S. Joo ◽  
Gretchen Meinke ◽  
Stephanie Moine ◽  
Elena N. Naumova ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Cell Cycle Progression ◽  
Cell Cycle Control ◽  
Cellular Proteins ◽  
Cycle Progression ◽  
Cellular Processes ◽  
Tumor Viruses ◽  
Cellular Pathways ◽  
Regulation Of Cell Cycle

ABSTRACT Studies of DNA tumor viruses have provided important insights into fundamental cellular processes and oncogenic transformation. They have revealed, for example, that upon expression of virally encoded proteins, cellular pathways involved in DNA repair and cell cycle control are disrupted. Herein, evidence is presented that BRCT-related regions are present in the helicase domains of the viral initiators encoded by the Polyomaviridae and Papillomaviridae viral families. Of interest, BRCT domains in cellular proteins recruit factors involved in diverse pathways, including DNA repair and the regulation of cell cycle progression. Therefore, the viral BRCT-related regions may compete with host BRCT domains for particular cellular ligands, a process that would help to explain the pleiotropic effects associated with infections with many DNA tumor viruses.

scholarly journals Vocal Fold Fibroblasts in Reinke’s Edema Show Alterations Involved in Extracellular Matrix Production, Cytokine Response and Cell Cycle Control

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 735
Author(s):  
Magdalena Grill ◽  
Isaac Lazzeri ◽  
Andrijana Kirsch ◽  
Nina Steurer ◽  
Tanja Grossmann ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Extracellular Matrix ◽  
Differential Expression ◽  
Vocal Fold ◽  
Expression Profiles ◽  
Cell Cycle Control ◽  
Vocal Folds ◽  
Gene Set Enrichment Analysis ◽  
Current Therapy ◽  
Reinke’S Edema

The voice disorder Reinke’s edema (RE) is a smoking- and voice-abuse associated benign lesion of the vocal folds, defined by an edema of the Reinke’s space, accompanied by pathological microvasculature changes and immune cell infiltration. Vocal fold fibroblasts (VFF) are the main cell type of the lamina propria and play a key role in the disease progression. Current therapy is restricted to symptomatic treatment. Hence, there is an urgent need for a better understanding of the molecular causes of the disease. In the present study, we investigated differential expression profiles of RE and control VFF by means of RNA sequencing. In addition, fast gene set enrichment analysis (FGSEA) was performed in order to obtain involved biological processes, mRNA and protein levels of targets of interest were further evaluated. We identified 74 differentially regulated genes in total, 19 of which were upregulated and 55 downregulated. Differential expression analysis and FGSEA revealed upregulated genes and pathways involved in extracellular matrix (ECM) remodeling, inflammation and fibrosis. Downregulated genes and pathways were involved in ECM degradation, cell cycle control and proliferation. The current study addressed for the first time a direct comparison of VFF from RE to control and evaluated immediate functional consequences.

scholarly journals A genetic interaction map of cell cycle regulators

2016 ◽  
Vol 27 (8) ◽  
pp. 1397-1407 ◽  
Author(s):  
Maximilian Billmann ◽  
Thomas Horn ◽  
Bernd Fischer ◽  
Thomas Sandmann ◽  
Wolfgang Huber ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Genetic Interaction ◽  
Interaction Analysis ◽  
Cell Cycle Control ◽  
Cell Cycle Regulators ◽  
Cellular Processes ◽  
A Genome ◽  
Interaction Map ◽  
Genome Scale ◽  
Genetic Interaction Analysis

Cell-based RNA interference (RNAi) is a powerful approach to screen for modulators of many cellular processes. However, resulting candidate gene lists from cell-based assays comprise diverse effectors, both direct and indirect, and further dissecting their functions can be challenging. Here we screened a genome-wide RNAi library for modulators of mitosis and cytokinesis in Drosophila S2 cells. The screen identified many previously known genes as well as modulators that have previously not been connected to cell cycle control. We then characterized ∼300 candidate modifiers further by genetic interaction analysis using double RNAi and a multiparametric, imaging-based assay. We found that analyzing cell cycle–relevant phenotypes increased the sensitivity for associating novel gene function. Genetic interaction maps based on mitotic index and nuclear size grouped candidates into known regulatory complexes of mitosis or cytokinesis, respectively, and predicted previously uncharacterized components of known processes. For example, we confirmed a role for the Drosophila CCR4 mRNA processing complex component l(2)NC136 during the mitotic exit. Our results show that the combination of genome-scale RNAi screening and genetic interaction analysis using process-directed phenotypes provides a powerful two-step approach to assigning components to specific pathways and complexes.

scholarly journals FADD in Cancer: Mechanisms of Altered Expression and Function, and Clinical Implications

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1462 ◽  
Author(s):  
José L Marín-Rubio ◽  
Laura Vela-Martín ◽  
José Fernández-Piqueras ◽  
María Villa-Morales
Keyword(s):  
Posttranslational Modifications ◽  
Cell Cycle Control ◽  
Regulation Of Gene Expression ◽  
Death Receptor ◽  
Clinical Implications ◽  
Altered Expression ◽  
Cellular Processes ◽  
Potential Biomarker ◽  
And Function ◽  
And Control

FADD was initially described as an adaptor molecule for death receptor-mediated apoptosis, but subsequently it has been implicated in nonapoptotic cellular processes such as proliferation and cell cycle control. During the last decade, FADD has been shown to play a pivotal role in most of the signalosome complexes, such as the necroptosome and the inflammasome. Interestingly, various mechanisms involved in regulating FADD functions have been identified, essentially posttranslational modifications and secretion. All these aspects have been thoroughly addressed in previous reviews. However, FADD implication in cancer is complex, due to pleiotropic effects. It has been reported either as anti- or protumorigenic, depending on the cell type. Regulation of FADD expression in cancer is a complex issue since both overexpression and downregulation have been reported, but the mechanisms underlying such alterations have not been fully unveiled. Posttranslational modifications also constitute a relevant mechanism controlling FADD levels and functions in tumor cells. In this review, we aim to provide detailed, updated information on alterations leading to changes in FADD expression and function in cancer. The participation of FADD in various biological processes is recapitulated, with a mention of interesting novel functions recently proposed for FADD, such as regulation of gene expression and control of metabolic pathways. Finally, we gather all the available evidence regarding the clinical implications of FADD alterations in cancer, especially as it has been proposed as a potential biomarker with prognostic value.

scholarly journals The Role of Chaperone-Mediated Autophagy in Cell Cycle Control and Its Implications in Cancer

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2140
Author(s):  
Marina Andrade-Tomaz ◽  
Izadora de Souza ◽  
Clarissa Ribeiro Reily Rocha ◽  
Luciana Rodrigues Gomes
Keyword(s):  
Cell Cycle ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cell Cycle Control ◽  
Hypoxia Inducible Factor ◽  
Cellular Processes ◽  
Hypoxia Inducible Factor 1 ◽  
Chaperone Mediated Autophagy ◽  
Transformation Processes

The cell cycle involves a network of proteins that modulate the sequence and timing of proliferation events. Unregulated proliferation is the most fundamental hallmark of cancer; thus, changes in cell cycle control are at the heart of malignant transformation processes. Several cellular processes can interfere with the cell cycle, including autophagy, the catabolic pathway involved in degradation of intracellular constituents in lysosomes. According to the mechanism used to deliver cargo to the lysosome, autophagy can be classified as macroautophagy (MA), microautophagy (MI), or chaperone-mediated autophagy (CMA). Distinct from other autophagy types, CMA substrates are selectively recognized by a cytosolic chaperone, one-by-one, and then addressed for degradation in lysosomes. The function of MA in cell cycle control, and its influence in cancer progression, are already well-established. However, regulation of the cell cycle by CMA, in the context of tumorigenesis, has not been fully addressed. This review aims to present and debate the molecular mechanisms by which CMA can interfere in the cell cycle, in the context of cancer. Thus, cell cycle modulators, such as MYC, hypoxia-inducible factor-1 subunit alpha (HIF-1α), and checkpoint kinase 1 (CHK1), regulated by CMA activity will be discussed. Finally, the review will focus on how CMA dysfunction may impact the cell cycle, and as consequence promote tumorigenesis.

scholarly journals Emerging concepts of nucleolar assembly

2002 ◽  
Vol 115 (11) ◽  
pp. 2265-2270 ◽  
Author(s):  
Danièle Hernandez-Verdun ◽  
Pascal Roussel ◽  
Jeannine Gébrane-Younès
Keyword(s):  
Cell Cycle ◽  
Ribosome Biogenesis ◽  
Cell Cycle Progression ◽  
Cell Cycle Control ◽  
Cycle Progression ◽  
Cooperative Interactions ◽  
Cellular Processes ◽  
Nuclear Domain ◽  
New Ideas

The nucleolus is a large nuclear domain and the site of ribosome biogenesis. It is also at the parting of the ways of several cellular processes, including cell cycle progression, gene silencing, and ribonucleoprotein complex formation. Consequently, a functional nucleolus is crucial for cell survival. Recent investigations of nucleolar assembly during the cell cycle and during embryogenesis have provided an integrated view of the dynamics of this process. Moreover, they have generated new ideas about cell cycle control of nucleolar assembly, the dynamics of the delivery of the RNA processing machinery, the formation of prenucleolar bodies, the role of precursor ribosomal RNAs in stabilizing the nucleolar machinery and the fact that nucleolar assembly is completed by cooperative interactions between chromosome territories. This has opened a new area of research into the dynamics of nuclear organization and the integration of nuclear functions.

scholarly journals Targeted Therapy-Resistant Melanoma Cells Acquire Transcriptomic Similarities with Human Melanoblasts

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 451 ◽  
Author(s):  
Lionel Larribère ◽  
Silke Kuphal ◽  
Christos Sachpekidis ◽  
Sachindra ◽  
Laura Hüser ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Damage Control ◽  
Cell Cycle Control ◽  
Melanoma Cells ◽  
In Vitro Models ◽  
Acquired Drug Resistance ◽  
Expression Of Genes ◽  
Induced Pluripotent ◽  
Or Genes

The mechanisms of adaptive and acquired drug resistance in tumors are not completely understood. So far, gene amplifications or mutations, leading to the reactivation of the MAPK or PI3K pathways have been described. In this study, we used two different methods to generate human melanoblasts: (1) via differentiation from induced pluripotent stem cells (iPSCs) and (2) via dedifferentiation from melanocytes. The melanoblast transcriptomes were then compared to the transcriptome of MAPK inhibitor-resistant melanoma cells. We observed that the expression of genes associated with cell cycle control, DNA damage control, metabolism, and cancer was altered in both melanoblast populations and in both adaptive and acquired resistant melanoma samples, compared to drug-sensitive samples. However, genes involved in antigen presentation and cellular movement were only regulated in the melanoblast populations and in the acquired resistant melanoma samples, compared to the drug-sensitive samples. Moreover, melanocyte-derived melanoblasts and adaptive resistant melanoma samples were characterized by different expression levels of certain transcription factors or genes involved in the CDK5 pathway. In conclusion, we show here that in vitro models of human melanoblasts are very important tools to comprehend the expression profiles of drug-resistant melanoma.

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