The Mechanism of Nano-Particles Intervening Invasion and Metastasis of Lymphoma Based on Autophagy Targeted with miR-36b and Orienteering Analysis on Apoptosis Gene

2021 ◽  
Vol 11 (11) ◽  
pp. 2306-2312
Author(s):  
Guihua Zhao ◽  
Xiaoying Ma ◽  
Dejun Sun
Keyword(s):  
Normal Cell ◽  
P53 Protein ◽  
Lymphoma Cell ◽  
Cell Strain ◽  
Nano Particles ◽  
Control Group ◽  
Proliferative Capacity ◽  
Invasion And Metastasis ◽  
Apoptosis Gene ◽  
P53 Mrna

Whether the expression of gene P53 related with autophagy and apoptosis and action was regulated by miR-36b was discussed in our study. And the action of orienteering nano-particles on intervening invasion and metastasis of lymphoma was analyzed. The normal lymphoid tissue collected from the patients with simple lymphatic hyperplasia was set as control. The lymphoma samples from patients with early indolent lymphoma were collected. The level of mRNA in miR-36b and P53 was detected by PCR. The level of P53 protein and level of mRNA in miR-36b and P53 among normal lymphoid cell, cell strain of low metastatic lymphoma and cell strain of high metastatic lymphoma was compared. They were divided into four groups: miR-NC group, orienteering nano-particles’ group, siRNA-NC group and siRNA-P53 group. The cell proliferative capacity was detected by FCM. The quantity of cell invasion and metastasis was detected by transwell. The expression quantity of P53 mRNA in lymphoma tissue was increased obviously compared with control group. The expression of miR-36b was lower while the expression of P53 was higher along with the later staging of TNM. And the express was related with the staging of TNM. The expression quantity of P53 mRNA in lymphoma cell was higher in normal cell notably. But expression quantity of miR-36b in lymphoma cell was lower in normal cell notably. The decreased of expression of miR-36b and increased of expression of P53 was related with enhancing the ability of invasion and metastasis of lymphoma cells.

scholarly journals Inhibition of polyamine synthesis induces p53 gene expression but not apoptosis

1999 ◽  
Vol 276 (4) ◽  
pp. C946-C954 ◽  
Author(s):  
Li Li ◽  
Ji Li ◽  
Jaladanki N. Rao ◽  
Minglin Li ◽  
Barbara L. Bass ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Inhibition ◽  
P53 Protein ◽  
Specific Inhibitor ◽  
P53 Gene ◽  
Mrna Levels ◽  
Intestinal Epithelial ◽  
Polyamine Biosynthesis ◽  
Fetal Bovine ◽  
P53 Mrna

The nuclear phosphoprotein p53 acts as a transcription factor and is involved in growth inhibition and apoptosis. The present study was designed to examine the effect of decreasing cellular polyamines on p53 gene expression and apoptosis in small intestinal epithelial (IEC-6) cells. Cells were grown in DMEM containing 5% dialyzed fetal bovine serum in the presence or absence of α-difluoromethylornithine (DFMO), a specific inhibitor of polyamine biosynthesis, for 4, 6, and 12 days. The cellular polyamines putrescine, spermidine, and spermine in DFMO-treated cells decreased dramatically at 4 days and remained depleted thereafter. Polyamine depletion by DFMO was accompanied by a significant increase in expression of the p53 gene. The p53 mRNA levels increased 4 days after exposure to DFMO, and the maximum increases occurred at 6 and 12 days after exposure. Increased levels of p53 mRNA in DFMO-treated cells were paralleled by increases in p53 protein. Polyamines given together with DFMO completely prevented increased expression of the p53 gene. Increased expression of the p53 gene in DFMO-treated cells was associated with a significant increase in G1 phase growth arrest. In contrast, no features of programmmed cell death were identified after polyamine depletion: no internucleosomal DNA fragmentation was observed, and no morphological features of apoptosis were evident in cells exposed to DFMO for 4, 6, and 12 days. These results indicate that 1) decreasing cellular polyamines increases expression of the p53 gene and 2) activation of p53 gene expression after polyamine depletion does not induce apoptosis in intestinal crypt cells. These findings suggest that increased expression of the p53 gene may play an important role in growth inhibition caused by polyamine depletion.

scholarly journals Allosteric changes in HDM2 by the ATM phosphomimetic S395D mutation: implications on HDM2 function

2019 ◽  
Vol 476 (21) ◽  
pp. 3401-3411 ◽  
Author(s):  
Lukas Uhrik ◽  
Lixiao Wang ◽  
Lucia Haronikova ◽  
Ixaura Medina-Medina ◽  
Yolanda Rebolloso-Gomez ◽  
...  
Keyword(s):  
Ataxia Telangiectasia ◽  
P53 Protein ◽  
Intrinsic Disorder ◽  
26S Proteasome ◽  
Ataxia Telangiectasia Mutated ◽  
Cellular Functions ◽  
Post Translational Modifications ◽  
Protein Protein Interaction ◽  
Positive Regulator ◽  
P53 Mrna

Allosteric changes imposed by post-translational modifications regulate and differentiate the functions of proteins with intrinsic disorder regions. HDM2 is a hub protein with a large interactome and with different cellular functions. It is best known for its regulation of the p53 tumour suppressor. Under normal cellular conditions, HDM2 ubiquitinates and degrades p53 by the 26S proteasome but after DNA damage, HDM2 switches from a negative to a positive regulator of p53 by binding to p53 mRNA to promote translation of the p53 mRNA. This change in activity is governed by the ataxia telangiectasia mutated kinase via phosphorylation on serine 395 and is mimicked by the S395D phosphomimetic mutant. Here we have used different approaches to show that this event is accompanied by a specific change in the HDM2 structure that affects the HDM2 interactome, such as the N-termini HDM2–p53 protein–protein interaction. These data will give a better understanding of how HDM2 switches from a negative to a positive regulator of p53 and gain new insights into the control of the HDM2 structure and its interactome under different cellular conditions and help identify interphases as potential targets for new drug developments.

scholarly journals Application of Magnetic Resonance Image Intelligent Data Acquisition in Ovarian Cancer (Preprint)

2020 ◽  
Author(s):  
Tingting Liang ◽  
Yanlei Dong ◽  
Xinrui Zhao ◽  
Lu Wang ◽  
Hui Xu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Magnetic Resonance ◽  
Epithelial Cells ◽  
Data Acquisition ◽  
Cell Lines ◽  
P53 Protein ◽  
Control Group ◽  
Ovarian Epithelial Cells ◽  
Intelligent Data Acquisition ◽  
Experimental Group

UNSTRUCTURED As a diagnostic method with no radiation, high resolution of soft tissue, and different imaging methods, Magnetic Resonance Imaging (MRI) intelligent data acquisition is more and more widely used in the examination of abdominal, pelvic, and other organ lesions. In order to study the diagnostic effect of multi-mode magnetic resonance intelligent data acquisition on ovarian cancer and the ovarian cancer model modified based on p53-/-+Myc+ASAP1 gene, NSG mice were selected as experimental subjects in this study. 293FT cell lines packaging p53, Myc, and ASAP1(ArfGAP with SH3 domain, Ankyrin repeat and PH domain 1) recombinant lentivirus were inoculated into mouse ovarian epithelial cells to construct mouse ovarian epithelial cell tumor cell lines and their performance was analyzed. According to the different injection cell lines, they were divided into the experimental group and the control group. Tumor samples were collected and the mice were analyzed using immunofluorescence staining and MRI. The results showed that, in the detection of protein expression in genetically modified cell lines, for p53-/-+Myc+ASAP1 fully modified cell lines, the high expression of ASAP1 and Myc functional proteins was detected after the lentivirus containing p53-/-, ASAP1, and Myc were introduced into mouse ovarian epithelial cells, while the expression of p53 protein decreased significantly; after inoculation into mice, it was found that the expression of ASAP1 protein and Myc protein in the experimental group was significantly higher than that in the control group, while the expression of p53 protein in the experimental group was significantly lower than that in the control group, with significant statistical difference; further MRI diagnosis of two groups of mice showed that the ADC (Apparent dispersion coefficient) value of the experimental group was significantly higher than the control group, there were statistically significant differences. Therefore, it was found that p53 gene expression was down-regulated and Myc and ASAPl genes were overexpressed in the tumor tissues and tumor cells formed, and tumor formation differences between the two groups of mice could be obviously found after MRI intelligent data acquisition, which provided experimental basis for early diagnosis of breast cancer in the later clinical stage.

Telomerase and immortalization

2019 ◽  
pp. 209-220
Author(s):  
Laura Collopy ◽  
Kazunori Tomita
Keyword(s):  
Cell Cycle ◽  
Growth And Development ◽  
Normal Cell ◽  
Chromosome Instability ◽  
Growth Arrest ◽  
Proliferative Capacity ◽  
Differentiated Cells ◽  
Dividing Cells ◽  
History Of ◽  
A Cell

The lifetime of a cell is set by the terminal ends of our chromosomes, ageing timers called telomeres. Most dividing cells, not exceptional for cancers, require telomeres to protect chromosomes. However, telomere erosion occurs at every cell cycle, thus imposing a proliferative capacity, eventually triggering a growth arrest. Cancer cells must overcome this proliferative limit in order to continue dividing. In the vast majority of cases, the growth and progression of cancers correlates with the upregulation of telomerase, an enzyme that replenishes telomeres. Telomerase is not active in normal, differentiated cells and its reactivation in cancer renders cells immortal and promotes their continued growth and development. Curiously, in cancer telomerase maintains short telomeres, retaining chromosome instability. Here, we briefly take you through history of cellular mortality with the connection to telomeres and telomerase and review their function in the normal cell to address their role during the transformation to malignancy.

scholarly journals A single synonymous mutation determines the phosphorylation and stability of the nascent protein

2018 ◽  
Vol 11 (3) ◽  
pp. 187-199 ◽  
Author(s):  
Konstantinos Karakostis ◽  
Sivakumar Vadivel Gnanasundram ◽  
Ignacio López ◽  
Aikaterini Thermou ◽  
Lixiao Wang ◽  
...  
Keyword(s):  
Ribosomal Proteins ◽  
P53 Protein ◽  
Intrinsically Disordered Protein ◽  
Subcellular Location ◽  
Genotoxic Stress ◽  
Synonymous Mutation ◽  
Atm Kinase ◽  
Intrinsically Disordered ◽  
The Stability ◽  
P53 Mrna

Abstract p53 is an intrinsically disordered protein with a large number of post-translational modifications and interacting partners. The hierarchical order and subcellular location of these events are still poorly understood. The activation of p53 during the DNA damage response (DDR) requires a switch in the activity of the E3 ubiquitin ligase MDM2 from a negative to a positive regulator of p53. This is mediated by the ATM kinase that regulates the binding of MDM2 to the p53 mRNA facilitating an increase in p53 synthesis. Here we show that the binding of MDM2 to the p53 mRNA brings ATM to the p53 polysome where it phosphorylates the nascent p53 at serine 15 and prevents MDM2-mediated degradation of p53. A single synonymous mutation in p53 codon 22 (L22L) prevents the phosphorylation of the nascent p53 protein and the stabilization of p53 following genotoxic stress. The ATM trafficking from the nucleus to the p53 polysome is mediated by MDM2, which requires its interaction with the ribosomal proteins RPL5 and RPL11. These results show how the ATM kinase phosphorylates the p53 protein while it is being synthesized and offer a novel mechanism whereby a single synonymous mutation controls the stability and activity of the encoded protein.

siRNA Targeting bcl-2 Gene Improve H and RA Drug-Sensitivity in HL-60 Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4369-4369
Author(s):  
Haiyan Hu ◽  
Yuan Zhang ◽  
Guo Kunyuan
Keyword(s):  
Membrane Potential ◽  
Drug Sensitivity ◽  
Calf Serum ◽  
Control Group ◽  
Small Interference Rna ◽  
Mtt Method ◽  
Cultural Medium ◽  
Apoptosis Gene ◽  
And Control ◽  
Cell Proliferations

Abstract The anti-apoptosis gene, bcl-2, is also related to drug-resistance, which expresses markedly higher on all kinds of leukemia. small interference RNA can silence the targeted mRNA expression. Objective: To study the effect of G3139 and siRNA targeting bcl-2 gene which increase the sensitivity of HL-60 cell to HT, Ara-C, As2O3 and RA. Method:Incubate leukima cell HL-60 with H, Ara-C, As2O3 and RA, meanwhile transfected siRNAs or G3139 in it by lipofectamine2000 with OPTI-MEM cultural medium for 6h, then add equal volume RPMI-1640 culture medium containing 20% inactive newborn calf serum. After transfection for 24,48 and 72h, cell proliferations were determined by MTT method. After transfection for 48h, we test the level of Bcl-2 protein, ROS and membrane potential of mitochondrion in HL-60 cell by FCM. Result: Compare with control group, the G3139 and siRNA targeting bcl-2 combine with H or Ara-C or As2O3 have significant effects on inhibiting the proliferation of HL-60(P <0.05); After transfecting 48h, the level of Bcl-2 protein and ROS decrease significantly, meanwhile membrane potential of mitochondrion in HL-60 cells increase markedly (P<0.01). Compare with control group, the G3139 and siRNA targeting bcl-2 combine with RA have significant effects on inhibiting the proliferation of HL-60 and the level of Bcl-2 protein decrease, but there were not difference between test groups and control group on the level of ROS and membrane potential of mitochondrion (P<0.01). Conclusion: The effective siRNA2, targeting bcl-2, can increased the drug-sensitivity though inhibiting the expression of Bcl-2 protein. Different drug has different mechanism to induce the leukimic cell apoptosis.

Motexafin Gadolinium (MGD) Induces Oxidant Stress and Downregulates Both Pro and Anti-Oxidant Genes in the Ramos Lymphoma Cell Line: Signaling through p53 Mediated Pathways.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4429-4429
Author(s):  
Amareshwar T.K. Singh ◽  
Andrew M. Evens ◽  
Qudsia Haque ◽  
Sheila N. Prachand ◽  
Karthik T.K. Singh ◽  
...  
Keyword(s):  
Cell Line ◽  
P53 Protein ◽  
Oxidant Stress ◽  
Free Water ◽  
Lymphoma Cell ◽  
Lymphoma Cell Line ◽  
Post Translational Modification ◽  
Redox Stress ◽  
Antioxidant Genes ◽  
Mdm2 Inhibitor

Abstract We have reported that MGd, an expanded porphyrin and redox stress inducer, lowers p53 protein but not message in lymphoma cell lines. These results suggested that there is post-translational modification of p53 induced by MGd, and that this effect depends on the presence of ascorbate (Asc) or zinc (Zn). To expand these earlier studies, we measured the expression of oxidant and antioxidant genes in Ramos (Burkitt’s) cells. We incubated Ramos cells for 5 hours with MGd 100μM with or without Zn acetate (Zn, 100μM), Asc 100μM, and Nutlin-3 15μM. Following incubation, total RNA was isolated by the Qiagen method and dissolved in RNase-free water. 1.0 μg RNA was used for reverse transcription using the Taq DNA polymerase system. PCR amplification was performed at 94°C for 30 sec (denaturation), 55°C (annealing) and 72°C (extension) for 35 cycles. This was followed by an extension at 72°C for 10 minutes. Anti-sense primers and sense primers for SESN1(T2), SESN2, GPX1, CDKN1A, and PP1A were used and DNA was identified by 1% agarose gel electrophoresis. The T2 transcript of SESN1 gene was absent in these cells. Co-treatment of MGd/Zn/Asc notably decreased GPX1, SESN2, and CDKN1A transcripts. To determine the role of p53 in the regulation of downstream redox targets, we added the MDM2 inhibitor, Nutlin-3. We found that GPX1, SESN2, and CDKN1A were restored with Nutlin-3. In addition, we measured another downstream target of p53, PUMA, in both Ramos and HF-1 cells (a follicular lymphoma cell line) by immunoblot after MGd, Zn, and Asc exposure in the presence or absence of Nutlin-3. PUMAα and PUMAβ isoforms returned to near baseline levels in the presence of Nutlin-3. The restoration of PUMA was more pronounced in HF-1 cells than in Ramos. In summary, then, we have shown that: the MDM2 inhibitor, Nutlin-3 reversed the downregulation of SESN2, GPX1, and CDKN1A genes that occurred as a result of MGd/Zn/Asc in Ramos cells and similarly, PUMAα and β isoforms were restored with Nutlin-3 after decreased expression following exposure to MGd, zinc, and ascorbate. These data indicate that some MGd-mediated signaling events in lymphoma cells are mediated through p53-dependent pathways.

Inhibition Effects of baicalin on Lymphoma Cell Line CA46 in Vitro and in Vivo

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5053-5053
Author(s):  
Jian Da Hu ◽  
Yi Huang ◽  
Yingyu Chen ◽  
Tiannan Wei ◽  
Tingbo Liu ◽  
...  
Keyword(s):  
Cell Line ◽  
Biological Effects ◽  
Annexin V ◽  
Lymphoma Cell ◽  
Control Group ◽  
Dependent Manner ◽  
Lymphoma Cell Line ◽  
Proliferation Inhibition

Abstract Baicalin is a traditional Chinese medicine with multiple biological effects. Some researches showed baicalin has anti-tumor effects in solid tumor, such as prostate cancer. In order to investigate its effects on proliferation inhibition and apoptosis induction in human lymphoma cell, we treated Burkitt lymphoma cell line CA46 with baicalin in vitro and in vivo of CA46 xenograft. Baicalin remarkably inhibited the cell proliferation, with an IC50 value of 10μM. Apoptosis was remarkably induced by baicalin in a dose-dependent manner, which was detected by Annexin V FITC/PI double staining analysis, TUNEL labeling method and DNA fragmentation respectively. Furthermore, RT-PCR showed that the mRNA expressions of c-myc and bcl-2 in treated CA46 cell decreased in a time-dependent manner. Western-Blot showed that the protein expressions of c-myc, bcl-2, procaspase-3 and PARP(116KD) in baicalin treated CA46 cell were down-regulated, while the expression of PARP(85KD) increased. Based on the results in vitro, we investigated in vivo efficacy of baicalin, alone or in combination with cytotoxic drug VP16, for treatment in CA46 nude mice xenograft. Baicalin with the dosage of 40mg/kg/d and 80kg/mg/d could remarkably inhibit the growth of the tumor compared with control group. Combination of baicalin and VP16 had better anti-tumor effects. Histological examination of tumor samples showed more necrotic cells in treated groups. And obvious apoptosis could be observed by electron microscope. No adverse events were found in treated groups. From above we could conclude that baicalin could efficiently induce proliferation inhibition and apoptosis of CA46 cells in vitro and in vivo, which may be related with the down-regulation of c-myc and bcl-2 expressions, as well as the up-regulation of caspase-3 activity.

scholarly journals Abelson murine leukemia virus-transformed cells that lack p53 protein synthesis express aberrant p53 mRNA species.

1984 ◽  
Vol 4 (3) ◽  
pp. 552-558 ◽  
Author(s):  
D Wolf ◽  
S Admon ◽  
M Oren ◽  
V Rotter
Keyword(s):  
Murine Leukemia Virus ◽  
P53 Protein ◽  
Leukemia Virus ◽  
Transformed Cells ◽  
Mrna Species ◽  
Abelson Murine Leukemia Virus ◽  
Polyadenylated Mrna ◽  
Murine Leukemia ◽  
Specific Mrna ◽  
P53 Mrna

Cells of the Abelson murine leukemia virus-transformed line L12 that lack the p53 protein also lack polyadenylated mRNA capable of directing the synthesis of p53 in a cell-free system. Direct analysis of stable polyadenylated mRNA from a variety of cell lines shows that all p53 producers shared a common mRNA species (2.0 kilobases) which hybridized with a p53-specific cDNA probe. This species, which appears to be the mature, normal-sized p53 mRNA, was totally undetectable in L12 cells, which did not produce p53 in vivo. However, L12 cells contained two major p53-specific mRNA species of a substantially larger size (3.5 and 6.5 kilobases) than the p53-specific mRNA in the p53-producing cells. Genomic DNA analysis uncovered an apparent alteration in the 5' proximal part of only one p53 gene, which is unique to the L12 cell line. It is thus possible that the nonproducer phenotype of L12 cells is due at least in part to an alteration within a p53-specific DNA sequence. These findings define a system in which production of p53 appears to be efficiently regulated at the level of stable mRNA and which can be used to study the mechanisms controlling p53 expression in Abelson murine leukemia virus-transformed cells.

scholarly journals THE ACTIVITY OF APOPTOSIS AND PREMATURE AGING IN YOUNGAND MIDDLE-AGED MAN WITH POLYMORBID CARDIOVASCULAR DISEASEAND NON-PSYCHOTIC MENTAL DISORDERS

2017 ◽  
Vol 9 (1) ◽  
pp. 48-53
Author(s):  
A S Partsernyak ◽  
M A Aflitonov ◽  
Y Sh Khalimov ◽  
E B Kireeva ◽  
A N Mironenko ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Protein Level ◽  
Standard Therapy ◽  
P53 Protein ◽  
Test Methods ◽  
Functional Class ◽  
Premature Aging ◽  
Control Group ◽  
Second Phase ◽  
The Third

Objective: To study the activity of apoptosis and premature aging in individuals of middle age with polymorbidity cardiovascular disease and non-psychotic mental disorders.Design and methods: The study included 78 men with MCVP and 20 healthy men. used in the study: complex psychological test methods and laboratory-instrumental evaluation of the cardiovascular system. definition p53 protein was performed by ELISA using kits BMS eBioscience BMS256 (BenderMedSys- tems, uSA). Results: n the group of patients with polymorbidity cardiovascular disease (PTS) of the p53 protein level was 4,89 uI / ml in the control group, p53 0,93 uI / ml. In all groups celebrated the acceler- ated pace of aging by an average of 10 years, compared with the control group. In the second phase of the study, patients were divided into three groups, depending on the planned treatment scheme. In the group of patients treated with standard therapy of p53 protein level was 3,51 uI / ml, from the group comprising in addition to standard therapy, psychotherapy - 2,34 uI / ml, in the third group, where the methodology of psycho-physiological and psychological visual and auditory correction - 1 8 uI / ml. After a course of treatment in all groups showed slowing premature aging . The first and second groups , a transition of V in class IV , the third group III to V of the functional class of aging . during the correlation analysis it was found a strong correlation between p53 protein and BV (r + 0,69; p < 0.05).Conclusions: Patients with polymorbidity cardiovascular disease marked increase in titer of apop- tosis protein p53 , accelerating premature aging 7-10 years. A direct correlation between p53 protein and biological age (r + 0,69; p < 0.05). Against the background of complex treatment with standard therapy with psycho-physiological and psychological visual and auditory correction decreased prema- ture aging, as compared with the groups that used the standard therapy for 8-10 years.

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