scholarly journals Mining the Prognostic Value of HNRNPAB and Its Function in Breast Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Yun Cao ◽  
Wei Zhang ◽  
Yi-Ting Jin ◽  
Qiang Zou
Keyword(s):  
Phase Transition ◽  
Breast Carcinoma ◽  
Survival Rates ◽  
Bioinformatic Analysis ◽  
Strongly Correlated ◽  
M Phase ◽  
Elevated Expression ◽  
Heterogeneous Nuclear Ribonucleoproteins ◽  
Coexpressed Genes

Heterogeneous nuclear ribonucleoproteins (HNRNPs) are crucial members in the pathogenesis and progression of numerous cancers. However, the expression pattern and clinical significance of HNRNPs in breast carcinoma (BC) remain to be investigated. In the present study, bioinformatic analysis identified HNRNPAB as the only commonly upregulated HNRNP in BC. Elevated expression of HNRNPAB was positively associated with more aggressive diseases and poorer survival rates in BC. Pathway analysis revealed that HNRNPAB coexpressed genes were enriched in the pathway of G2/M phase transition, and the expression level of HNRNPAB was strongly correlated with those of CCNB1, CDK1, CDC25A, and CDC25C. Experiments in vitro demonstrated that HNRNPAB knockdown suppressed cell proliferation and blocked the G2/M phase transition in BC. Taken together, this study provides the initial evidence that HNRNPAB may be employed as an innovative therapeutic target as well as a prognostic biomarker in BC patients.

The Polo-like kinase Plx1 is a component of the MPF amplification loop at the G2/M-phase transition of the cell cycle in Xenopus eggs

1998 ◽  
Vol 111 (12) ◽  
pp. 1751-1757 ◽  
Author(s):  
A. Abrieu ◽  
T. Brassac ◽  
S. Galas ◽  
D. Fisher ◽  
J.C. Labbe ◽  
...  
Keyword(s):  
Phase Transition ◽  
Cell Cycle ◽  
Cyclin A ◽  
Cyclin B ◽  
Cdc2 Kinase ◽  
C Terminus ◽  
M Phase ◽  
Egg Extracts ◽  
Amplification Loop

We have investigated whether Plx1, a kinase recently shown to phosphorylate cdc25c in vitro, is required for activation of cdc25c at the G2/M-phase transition of the cell cycle in Xenopus. Using immunodepletion or the mere addition of an antibody against the C terminus of Plx1, which suppressed its activation (not its activity) at G2/M, we show that Plx1 activity is required for activation of cyclin B-cdc2 kinase in both interphase egg extracts receiving recombinant cyclin B, and cycling extracts that spontaneously oscillate between interphase and mitosis. Furthermore, a positive feedback loop allows cyclin B-cdc2 kinase to activate Plx1 at the G2/M-phase transition. In contrast, activation of cyclin A-cdc2 kinase does not require Plx1 activity, and cyclin A-cdc2 kinase fails to activate Plx1 and its consequence, cdc25c activation in cycling extracts.

scholarly journals MicroRNA Let-7 targets AMPK and impairs hepatic lipid metabolism in offspring of maternal obese pregnancies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laís A. P. Simino ◽  
Carolina Panzarin ◽  
Marina F. Fontana ◽  
Thais de Fante ◽  
Murilo V. Geraldo ◽  
...  
Keyword(s):  
Maternal Obesity ◽  
Ex Vivo ◽  
Bioinformatic Analysis ◽  
Serum Glucose ◽  
Strongly Correlated ◽  
Metabolic Disturbances ◽  
Hepatic Lipid Metabolism ◽  
Newborn Mice ◽  
Protein Levels

AbstractNutritional status during gestation may lead to a phenomenon known as metabolic programming, which can be triggered by epigenetic mechanisms. The Let-7 family of microRNAs were one of the first to be discovered, and are closely related to metabolic processes. Bioinformatic analysis revealed that Prkaa2, the gene that encodes AMPK α2, is a predicted target of Let-7. Here we aimed to investigate whether Let-7 has a role in AMPKα2 levels in the NAFLD development in the offspring programmed by maternal obesity. Let-7 levels were upregulated in the liver of newborn mice from obese dams, while the levels of Prkaa2 were downregulated. Let-7 levels strongly correlated with serum glucose, insulin and NEFA, and in vitro treatment of AML12 with glucose and NEFA lead to higher Let-7 expression. Transfection of Let-7a mimic lead to downregulation of AMPKα2 levels, while the transfection with Let-7a inhibitor impaired both NEFA-mediated reduction of Prkaa2 levels and the fat accumulation driven by NEFA. The transfection of Let-7a inhibitor in ex-vivo liver slices from the offspring of obese dams restored phospho-AMPKα2 levels. In summary, Let-7a appears to regulate hepatic AMPKα2 protein levels and lead to the early hepatic metabolic disturbances in the offspring of obese dams.

scholarly journals LINC00518 Promotes Cell Proliferation by Regulating the Cell Cycle of Lung Adenocarcinoma Through miR-185-3p Targeting MECP2

2021 ◽  
Vol 11 ◽  
Author(s):  
Xu Han ◽  
Jixiang Wu ◽  
Yajun Zhang ◽  
Jianxiang Song ◽  
Zhan Shi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Lung Adenocarcinoma ◽  
Human Cancer ◽  
Survival Rates ◽  
Bioinformatic Analysis ◽  
Luciferase Reporter

Previous studies have shown that long intergenic non-protein coding RNA 00518 (LINC00518) are essential for the cell growth and metastasis of human cancer. However, the role of LINC00518 in lung adenocarcinoma (LUAD) is still unknown. This research put emphasis on the function of LINC00518 on the cell growth of LUAD. The lncRNA, miRNA and mRNA expression were measured by using qRT-PCR. Protein levels were measured by using Western blotting. CCK-8, colony formation assays and transwell assay were performed to evaluate the cell proliferation ability and invasion. Bioinformatic analysis and luciferase reporter assays were chosen to confirm the mechanism of LINC00518 in LUAD. We found that LINC00518 was highly expressed in LUAD specimens and the high-expression was negatively correlated with the overall survival rates. This finding was also proved in the LUAD cell lines. Through a series of in vitro and in vivo experiments, we proved that LICN00518 promoted the cell growth of LUAD by regulating the cell cycle. Moreover, LICN00518 upregulated the expression of MECP2 by mutagenesis of miR-185-3p. The results suggested that LICN00518 could be used as a survival indicator and potential therapeutic target for LUAD patients.

scholarly journals Modulated Electro-Hyperthermia Supports the Effect of Gemcitabine Both in Sensitive and Resistant Pancreas Adenocarcinoma Cell Lines

2021 ◽  
Vol 27 ◽  
Author(s):  
Gertrud Forika ◽  
Eva Kiss ◽  
Gabor Petovari ◽  
Titanilla Danko ◽  
Aron Bertram Gellert ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Kinase Inhibitor ◽  
Treatment Resistance ◽  
Inhibitory Effect ◽  
Ductal Adenocarcinoma ◽  
Phase Cell ◽  
M Phase ◽  
Elevated Expression ◽  
Cell Cycle Inhibition

The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is frequently associated to high treatment resistance. Gemcitabine (GEM) alone or in combination is the most used chemotherapy for unresecable PDACs. Here we studied whether modulated electro-hyperthermia (mEHT), a non-invasive complementary treatment, can support the effect of GEM on PDAC cells in vitro. The LD20 for the GEM-resistant Panc1 cells proved to be 200× higher than for the drug-sensitive Capan1. The mEHT alone caused significant apoptosis in Capan1 cultures as confirmed by the elevated SubG1 phase cell fraction and increased number of cleaved Caspase-3 positive cells 48 h after treatment, with an additive effect when GEM was used after hyperthermia. These were accompanied by reduced number of G1, S, and G2/M phase cells and elevated expression of the cyclin-dependent kinase inhibitor p21waf1 protein. In GEM-resistant Panc1 cells, an initial apoptosis was detected by flow cytometry 24 h after mEHT ± GEM treatment, which however diminished by 48 h at persistent number of cleaved Caspase-3 positive tumor cells. Though GEM monotherapy reduced the number of tumor progenitor colonies in Capan1 cell line, an additive colony inhibitory effect of mEHT was observed after mEHT + GEM treatment. The heat shock induced Hsp27 and Hsp70 proteins, which are known to sensitize PDAC cells to GEM were upregulated in both Capan1 and Panc1 cells 24 h after mEHT treatment. The level of E-Cadherin, a cell adhesion molecule, increased in Capan1 cells after mEHT + GEM treatment. In conclusion, in GEM-sensitive PDAC cells mEHT treatment alone induced cell death and cell cycle inhibition and improved GEM efficiency in combination, which effects were milder and short-term up to 24 h in the GEM-resistant Panc1 cells. Our data further support the inclusion of hyperthermia, in particular of mEHT, into the traditional oncotherapy regimens of PDAC.

Inactivation of the checkpoint kinase Cds1 is dependent on cyclin B-Cdc2 kinase activation at the meiotic G2/M-phase transition in Xenopus oocytes

2001 ◽  
Vol 114 (18) ◽  
pp. 3397-3406
Author(s):  
Tetsuya Gotoh ◽  
Keita Ohsumi ◽  
Tomoko Matsui ◽  
Haruhiko Takisawa ◽  
Takeo Kishimoto
Keyword(s):  
Phase Transition ◽  
Xenopus Oocytes ◽  
Cyclin B ◽  
Cdc2 Kinase ◽  
Kinase Activation ◽  
Immature Oocytes ◽  
Protein Levels ◽  
M Phase ◽  
G2 Phase

Checkpoint controls ensure chromosomal integrity through the cell cycle. Chk1 and Cds1/Chk2 are effector kinases in the G2-phase checkpoint activated by damaged or unreplicated DNA, and they prevent entry into M-phase through inhibition of cyclin B-Cdc2 kinase activation. However, little is known about how the effector kinases are regulated when the checkpoint is attenuated. Recent studies indicate that Chk1 is also involved in the physiological G2-phase arrest of immature Xenopus oocytes via direct phosphorylation and inhibition of Cdc25C, the activator of cyclin B-Cdc2 kinase. Bearing in mind the overlapping functions of Chk1 and Cds1, here we have studied the involvement of Xenopus Cds1 (XCds1) in the G2/M-phase transition of immature oocytes and the regulation of its activity during this period. Protein levels of XCds1 remained constant throughout oocyte maturation and early embryonic development. The levels of XCds1 kinase activity were high in immature oocytes and decreased at the meiotic G2/M-phase transition. Consistently, when overexpressed in immature oocytes, wild-type, but not kinase-deficient, XCds1 significantly delayed entry into M-phase after progesterone treatment. The inactivation of XCds1 depended on the activation of cyclin B-Cdc2 kinase, but not MAP kinase. Although XCds1 was not directly inactivated by cyclin B-Cdc2 kinase in vitro, XCds1 was inactivated by overexpression of cyclin B, which induces the activation of cyclin B-Cdc2 kinase without progesterone. Thus, the present study is the first indication of Cds1 activity in cells that are physiologically arrested at G2-phase, and of its downregulation at entry into M-phase.

Ultrastructural Changes in Three Different Mammalian Cells Following Ultraviolet Laser Irradiation

1972 ◽  
Vol 30 ◽  
pp. 350-351
Author(s):  
K. Shankar Narayan ◽  
Kailash C. Gupta ◽  
Tohru Okigaki
Keyword(s):  
Ultraviolet Light ◽  
Mammalian Cells ◽  
Biological Effects ◽  
Survival Rates ◽  
Chinese Hamster ◽  
Cell Types ◽  
Differential Sensitivity ◽  
Ultrastructural Changes ◽  
Ultraviolet Laser

The biological effects of short-wave ultraviolet light has generally been described in terms of changes in cell growth or survival rates and production of chromosomal aberrations. Ultrastructural changes following exposure of cells to ultraviolet light, particularly at 265 nm, have not been reported.We have developed a means of irradiating populations of cells grown in vitro to a monochromatic ultraviolet laser beam at a wavelength of 265 nm based on the method of Johnson. The cell types studies were: i) WI-38, a human diploid fibroblast; ii) CMP, a human adenocarcinoma cell line; and iii) Don C-II, a Chinese hamster fibroblast cell strain. The cells were exposed either in situ or in suspension to the ultraviolet laser (UVL) beam. Irradiated cell populations were studied either "immediately" or following growth for 1-8 days after irradiation.Differential sensitivity, as measured by survival rates were observed in the three cell types studied. Pattern of ultrastructural changes were also different in the three cell types.

a Novel Combinational Nanodrug Delivery System Induces Synergistic Inhibition of Lung Adenocarcinoma Cells in vitro

2020 ◽  
Vol 17 ◽  
Author(s):  
Mingliang Fan ◽  
Jiping Li
Keyword(s):  
Lung Adenocarcinoma ◽  
Delivery System ◽  
The Body ◽  
Anticancer Efficacy ◽  
Nanodrug Delivery ◽  
Drug Molecules ◽  
Cellular Assays ◽  
Lung Adenocarcinoma Cell Line ◽  
M Phase

Background: The combination of two or more therapeutic drugs is an attractive approach to improve the treatment of experimental tumors. Leveraging nanocarriers for combinational drug delivery can allow a control over drug biological fate and promote co-localization in the same area of the body. However, there are certain concerns regarding the biodegradability and potential long-term toxicity arising from these synthetic nanoscale carriers. Objective: Our aim was to develop a combinational nanodrug delivery system formed by self-assembling of amphiphilic drug molecules，minimizing potential toxicities associated with using additional synthetic nanocarriers. Methods: A novel prodrug chlorambucil gemcitabine conjugate was synthesized, this prodrug was used for the encapsulation of an additional hydrophobic anticancer drug paclitaxel, taking the form of combinational nanodrugs. Particle size and zeta potential were evaluated, cytotoxicity assay and apoptosis/cell cycle analysis were also performed to validate the anticancer efficacy of the combinational nanodrugs. Results: The combinational nanodrugs were acquired by means of nanoprecipitation. In A549 lung adenocarcinoma cell line, cellular assays revealed that co-delivery of low dosage paclitaxel with chlorambucil gemcitabine conjugate can act synergistically to inhibit cell growth and induce accumulation of cells in the G2/M phase with a concomitant decrease in G0/G1 compartment. Conclusion: Chlorambucil gemcitabine conjugate and paclitaxel can co-assemble into composite nanoparticles by a nanoprecipitation process and the resulting combinational nanodrugs showed synergistic anticancer effect. This synthetic nanocarrier-free approach might broaden the nanodrug concept and have potential in cancer therapy.

scholarly journals The roles and prognostic significance of ABI1-TSV-11 expression in patients with left-sided colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Zhang ◽  
Zhaohui Zhong ◽  
Mei Li ◽  
Jingyi Chen ◽  
Tingru Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
The Cancer Genome Atlas ◽  
Actin Dynamics ◽  
Elevated Expression ◽  
Sw480 Cells ◽  
And Migration

AbstractAbnormally expressed and/or phosphorylated Abelson interactor 1 (ABI1) participates in the metastasis and progression of colorectal cancer (CRC). ABI1 presents as at least 12 transcript variants (TSVs) by mRNA alternative splicing, but it is unknown which of them is involved in CRC metastasis and prognosis. Here, we firstly identified ABI1-TSV-11 as a key TSV affecting the metastasis and prognosis of left-sided colorectal cancer (LsCC) and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) in LsCC by analyzing data from The Cancer Genome Atlas and TSVdb. Secondly, ABI1-TSV-11 overexpression promoted LoVo and SW480 cells adhesion and migration in vitro, and accelerated LoVo and SW480 cells lung metastasis in vivo. Finally, mechanism investigations revealed that ABI1-isoform-11 interacted with epidermal growth factor receptor pathway substrate 8 (ESP8) and regulated actin dynamics to affect LoVo and SW480 cells biological behaviors. Taken together, our data demonstrated that ABI1-TSV-11 plays an oncogenic role in LsCC, it is an independent risk factor of prognosis and may be a potential molecular marker and therapeutic target in LsCC.

Sign in / Sign up

Export Citation Format

Share Document