scholarly journals Evidence for a Negative Correlation between Human Reactive Enamine-Imine Intermediate Deaminase A (RIDA) Activity and Cell Proliferation Rate: Role of Lysine Succinylation of RIDA

2021 ◽  
Vol 22 (8) ◽  
pp. 3804
Author(s):  
Luisa Siculella ◽  
Laura Giannotti ◽  
Benedetta Di Chiara Stanca ◽  
Matteo Calcagnile ◽  
Alessio Rochira ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Negative Correlation ◽  
Cancer Biology ◽  
Human Tumor ◽  
In Silico Analysis ◽  
Proliferation Rate ◽  
Reactive Intermediate ◽  
Cell Proliferation Rate

Reactive intermediate deaminase (Rid) proteins are enzymes conserved in all domains of life. UK114, a mammalian member of RidA subfamily, has been firstly identified as a component of liver perchloric acid-soluble proteins (L-PSP). Although still poorly defined, several functions have been attributed to the mammalian protein UK114/RIDA, including the reactive intermediate deamination activity. The expression of UK114/RIDA has been observed in some tumors, arousing interest in this protein as an evaluable tumor marker. However, other studies reported a negative correlation between UK114/RIDA expression, tumor differentiation degree and cell proliferation. This work addressed the question of UK114/RIDA expression in human non-tumor HEK293 cell lines and in some human tumor cell lines. Here we reported that human RIDA (hRIDA) was expressed in all the analyzed cell line and subjected to lysine (K-)succinylation. In HEK293, hRIDA K-succinylation was negatively correlated to the cell proliferation rate and was under the control of SIRT5. Moreover, K-succinylation clearly altered hRIDA quantification by immunoblotting, explaining, at least in part, some discrepancies about RIDA expression reported in previous studies. We found that hRIDA was able to deaminate reactive enamine-imine intermediates and that K-succinylation drastically reduced deaminase activity. As predicted by in silico analysis, the observed reduction of deaminase activity has been related to the drastic alterations of hRIDA structure inferred by K-succinylation. The role of hRIDA and the importance of its K-succinylation in cell metabolism, especially in cancer biology, have been discussed.

scholarly journals Interleukin4Rα (IL4Rα) and IL13Rα1 Are Associated with the Progress of Renal Cell Carcinoma through Janus Kinase 2 (JAK2)/Forkhead Box O3 (FOXO3) Pathways

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1394 ◽  
Author(s):  
Mi-Ae Kang ◽  
Jongsung Lee ◽  
Sang Ha ◽  
Chang Lee ◽  
Kyoung Kim ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Proliferation Rate ◽  
Janus Kinase ◽  
Janus Kinase 2 ◽  
Forkhead Box ◽  
Cell Proliferation Rate

Specific kinds of interleukin (IL) receptors are known to mediate lymphocyte proliferation and survival. However, recent reports have suggested that the high expression of IL4Rα and IL13Rα1 in tumor tissue might be associated with tumorigenesis in several kinds of tumor. We found that a significant association between mRNA level of IL4Rα or IL13Rα1 and the poor prognosis of renal cell carcinoma (RCC) from the public database (http://www.oncolnc.org/). Then, we evaluated the clinicopathological significance of the immunohistochemical expression of IL4Rα and IL13Rα1 in 199 clear cell RCC (CCRCC) patients. The individual and co-expression patterns of IL4Rα and IL13Rα1 were significantly associated with cancer-specific survival (CSS) and relapse-free survival (RFS) in univariate analysis. Multivariate analysis indicated IL4Rα-positivity and co-expression of IL4Rα and IL13Rα1 as the independent indicators of shorter CSS and RFS of CCRCC patients. For the in vitro evaluation of the oncogenic role of IL4Rα and IL13Rα1 in RCC, we knock-downed IL4Rα or IL13Rα1 and observed that the cell proliferation rate was decreased, and the apoptosis rate was increased in A498 and ACHN cells. Furthermore, we examined the possible role of Janus kinase 2 (JAK2), well-known down-stream tyrosine kinase under the heterodimeric receptor complex of IL4Rα and IL13Rα1. Interestingly, JAK2 interacted with Forkhead box O3 (FOXO3) to cause tyrosine-phosphorylation of FOXO3. Silencing IL4Rα or JAK2 in A498 and ACHN cells reduced the interaction between JAK2 and FOXO3. Moreover, pharmacological inhibition of JAK2 induced the nuclear localization of FOXO3, leading to increase apoptosis and decrease cell proliferation rate in A498 and ACHN cells. Taken together, these results suggest that IL4Rα and IL13Rα1 might be involved in the progression of RCC through JAK2/FOXO3 pathway, and their expression might be used as the novel prognostic factor and therapeutic target for RCC patients.

Polyploidization of Megakaryocyte Is Associated with the Proliferation Rate of Precursor Cell

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4802-4802
Author(s):  
Jianhui Wang ◽  
Michael A. Nardi ◽  
Zongdong Li
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Doubling Time ◽  
Kinase Inhibitor ◽  
Conflicts Of Interest ◽  
K562 Cells ◽  
Precursor Cell ◽  
Proliferation Rate ◽  
Cell Proliferation Rate ◽  
Highly Correlated

Abstract Abstract 4802 Endomitosis, the uncoupling of DNA replication with cytokinesis, occurs during the maturation of megakaryocytes (MK) and leads to the MK polyploidization (4N to 128N DNA content). The mechanism that controls the ploidy in MKs is not well understood. We investigated the correlation of cell proliferation rate with MK ploidy in several differentiating megakaryoblastic cell lines. Meg-01, CHRF-288, and K562 cells were treated with a Src kinase inhibitor (3 μm Su6656) for 4 days and the ploidy was assessed by propidium iodide. Proliferation rate was determined by the doubling time of synchronized cells cultured in 10% serum. We found a significant correlation between ploidy and proliferation rate in these cell lines, with the K562 line having both the highest proliferation rate and the percentage of ploidy cells. We then differentiated the megakaryocyte cell line L8057 cells by thrombopoietin using various concentrations of serum (5%, 10%, and 20%) to control proliferation. The proliferation rate of L8057 cells varied with serum concentration and was also highly correlated the percentage of ploidy cells (23%, 32.8%, and 40.9% respectively). Thus, our data suggest that factors control the cell proliferation rate may contribute to the polyploidization of megakaryocyte. Disclosures: No relevant conflicts of interest to declare.

scholarly journals c-Myc shuttled by tumour-derived extracellular vesicles promotes lung bronchial cell proliferation through miR-19b and miR-92a

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Cristina Borzi ◽  
Linda Calzolari ◽  
Anna M. Ferretti ◽  
Laura Caleca ◽  
Ugo Pastorino ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Patients ◽  
Cell Lines ◽  
Extracellular Vesicles ◽  
Target Genes ◽  
In Silico Analysis ◽  
Human Lung Cancer ◽  
Lung Cancer Patients

Abstract Lung cancer causes approximately one fifth of all cancer deaths. Tumour cells actively communicate with the surrounding microenvironment to support malignant progression. Extracellular vesicles (EVs) play a pivotal role in intercellular communication and modulate recipient cells by delivering their contents, including proteins and nucleic acids such as microRNAs (miRNAs). We isolated EVs from the conditioned medium (CM) of human lung cancer cell lines and plasma of lung cancer patients and cancer-free smokers using an ultracentrifugation method. A significant increase in bronchial HBEC-KRASV12high cell proliferation, confirmed by cell cycle analysis, was observed after treatment with cancer-derived EVs. Lung cancer-derived EVs induced transcription of the pri-miR-92a gene, resulting in the overexpression of mature miR-19b and miR-92a in recipient bronchial cells. Modulation of these two miRNAs using miRNA mimics or inhibitors confirmed their ability to promote proliferation. In silico analysis and experimental validation showed that miR-19b and miR-92a impaired the TGF-beta (TGFB) pathway and identified TGFBRI and TGFBRII as target genes involved in EV-mediated bronchial cell proliferation. Interestingly, the oncoprotein c-Myc, a well-known miR-17-92 cluster activator, was detected only in the EVs derived from lung cancer patients and cell lines and was able to modulate the proliferation of HBEC-KRASV12high recipient cells. These data support the role of c-Myc shuttling in lung cancer-derived EVs in inducing the upregulation of onco-miR-19b and miR-92a expression with concomitant impairment of the TGFB signalling pathway in recipient cells.

scholarly journals An Iodine Treatments Effect on Cell Proliferation Rates of Breast Cancer Cell Lines; In Vitro Study

2020 ◽  
Vol 8 (B) ◽  
pp. 1064-1070
Author(s):  
Aisyah Elliyanti ◽  
Veronika Y Susilo ◽  
Sri Setiyowati ◽  
Pasupuleti Visweswara Rao
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Proliferation Rate ◽  
Breast Cancer Cell Lines ◽  
Cell Proliferation Rate ◽  
Dose Dependent

BACKGROUND: Iodine can reduce breast tumor progression by mediates an antiproliferative effect. AIM: This study aimed to investigate the effect of iodine (I2), Lugol (I3K), and the combination of both on cell proliferation of three different types of breast cancer cell lines. METHODS: The samples were MCF7, SKBR3, and MDA-MB 213 cell lines. Cell proliferation rate was measured using colorimetric and clonogenic assays. RESULTS: The cell proliferation rate of MDA-MB 231 cells was reduced significantly by treatment I2, I3K, and combination of both with p = 0.046, p = 0.00, and p = 0.00, respectively. In MCF7 cells, I2 reduced the cell proliferation of 54–94% and I3K reduced the proliferation of 74–94%. The effectiveness of I3K treatments in slowing cell proliferation rate was dose-dependent. In SKBR3 cells, I2reduced proliferation cell up to 85% and I3K 4%-94% depending on the dose. Clonogenic assay results showed a discontinue of the cell proliferation by all doses of I2 and I3K (10 μM and 20 μM). CONCLUSION: Breast cancer cell lines, representing subtypes of luminal A, HER2+, and triple-negative, show an excellent response to iodine treatments and I3K response shows in a dose-dependent manner. Further studies are needed to investigate the effective in vivo doses.

scholarly journals Highly expressed SLCO1B3 inhibits the occurrence and development of breast cancer and can be used as a clinical indicator of prognosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiantian Tang ◽  
Guiying Wang ◽  
Sihua Liu ◽  
Zhaoxue Zhang ◽  
Chen Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines

AbstractThe role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.

scholarly journals Mass Spectrometry-Based Proteomic Characterization of Cutaneous Melanoma Ectosomes Reveals the Presence of Cancer-Related Molecules

2020 ◽  
Vol 21 (8) ◽  
pp. 2934 ◽  
Author(s):  
Magdalena Surman ◽  
Sylwia Kędracka-Krok ◽  
Dorota Hoja-Łukowicz ◽  
Urszula Jankowska ◽  
Anna Drożdż ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Content ◽  
Cell Lines ◽  
Cutaneous Melanoma ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Starting Point ◽  
Novel Biomarkers

Cutaneous melanoma (CM) is an aggressive type of skin cancer for which effective biomarkers are still needed. Recently, the protein content of extracellular vesicles (ectosomes and exosomes) became increasingly investigated in terms of its functional role in CM and as a source of novel biomarkers; however, the data concerning the proteome of CM-derived ectosomes is very limited. We used the shotgun nanoLC–MS/MS approach to the profile protein content of ectosomes from primary (WM115, WM793) and metastatic (WM266-4, WM1205Lu) CM cell lines. Additionally, the effect exerted by CM ectosomes on recipient cells was assessed in terms of cell proliferation (Alamar Blue assay) and migratory properties (wound healing assay). All cell lines secreted heterogeneous populations of ectosomes enriched in the common set of proteins. A total of 1507 unique proteins were identified, with many of them involved in cancer cell proliferation, migration, escape from apoptosis, epithelial–mesenchymal transition and angiogenesis. Isolated ectosomes increased proliferation and motility of recipient cells, likely due to the ectosomal transfer of different cancer-promoting molecules. Taken together, these results confirm the significant role of ectosomes in several biological processes leading to CM development and progression, and might be used as a starting point for further studies exploring their diagnostic and prognostic potential.

Cell proliferation rate and nuclear morphometry in Roberts syndrome

2008 ◽  
Vol 54 (6) ◽  
pp. 512-516 ◽  
Author(s):  
Petros M Pavlopoulos ◽  
Anastasia E Konstantinidou ◽  
Emmanuel Agapitos ◽  
Panagiotis Davaris
Keyword(s):  
Cell Proliferation ◽  
Proliferation Rate ◽  
Roberts Syndrome ◽  
Nuclear Morphometry ◽  
Cell Proliferation Rate

scholarly journals miR-940 potentially promotes proliferation and metastasis of endometrial carcinoma through regulation of MRVI1

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Zhan Zhou ◽  
Ya-Ping Xu ◽  
Li-Juan Wang ◽  
Yan Kong
Keyword(s):  
Cell Proliferation ◽  
Endometrial Carcinoma ◽  
Cell Lines ◽  
In Silico Analysis ◽  
Good Prognosis ◽  
The Cancer Genome Atlas ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Proliferation Ability ◽  
And Migration

AbstractThe specific functions and clinical significance of miR-940 in endometrial carcinoma (EC) have not been studied. First, we assessed the expression of miR-940 and MRVI1 in EC tissues collected from The Cancer Genome Atlas (TCGA) database and EC cell lines. miR-940 was significantly overexpressed in EC tissues and cell lines, particularly in RL95-2 cells. Correlation analysis showed that miR-940 expression level was remarkably associated with age, grade, and death. Moreover, the overall survival (OS) rate in the miR-940 low expression group was higher, compared with miR-940 high expression group. Univariate and multivariate models demonstrated that miR-940 expression, stage, and age were predictive indicators of OS. Moreover, there was no significance of the proliferation ability among the three EC cell lines (RL95-2, ISK, and KLE). To reveal the biological roles of miR-940, we respectively transfected RL95-2 cells with miR-940 mimics, miR-940 inhibitors, and control to further investigate the cell proliferation ability, and migration as well as invasion potential of RL95-2 cells. The transfection of miR-940 mimics significantly increased the proliferation and migration/invasion ability of RL95-2 cells. MRVI1 was predicted to be a potential target of miR-940 by means of in silico analysis followed by validation using luciferase reporter assays. MRVI1 was correlated with good prognosis. Moreover, forced expression of MRVI1 in miR-940 mimic transfected cells abolished the facilitation of miR-940 on cell proliferation, migration, and invasion of RL95-2 and KLE cells. In conclusion, our study demonstrates that miR-940 might function as a reliable diagnostic and prognostic signature in EC.

scholarly journals A New Sulfated Triterpene Saponin from Gypsophila trichotoma

2013 ◽  
Vol 8 (6) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Ilina Krasteva ◽  
Maya Yotova ◽  
Kristina Jenett-Siems ◽  
Petranka Zdraveva ◽  
Stefan Nikolov
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Cell Lines ◽  
Spectral Methods ◽  
Human Tumor ◽  
Malignant Cell ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Dependent Inhibition

A new sulfated triterpeniod saponin, 3- O-sulfooleanolic acid 28- O-[ β-glucopyranosyl-(1→3)]-[ β-glucopyranosyl-(1→6)]- β-glucopyranosyl ester (1), along with three known Δ7-sterols: stigmast-7-en-3 β-ol (2), stigmast-7-en-3- O-β-D-glucopyranoside (3) and stigmast-7-en-3-on (4) were isolated from the roots of Gypsophila trichotoma Wend. (Caryophyllaceae). Their structures were elucidated by chemical and spectral methods. Compound 1 caused concentration-dependent inhibition of malignant cell proliferation against different human tumor cell lines.

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