scholarly journals Hypoxia-Inducible Factor 1A Upregulates HMGN5 by Increasing the Expression of GATA1 and Plays a Role in Osteosarcoma Metastasis

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Enjie Xu ◽  
Zhe Ji ◽  
Heng Jiang ◽  
Tao Lin ◽  
Jun Ma ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Tumor Metastasis ◽  
Malignant Tumors ◽  
Hypoxia Inducible Factor ◽  
High Mobility ◽  
Migration And Invasion ◽  
Hypoxic Environment ◽  
The Relationship ◽  
Selection Of ◽  
Cells Cultured

Osteosarcoma is one of the most common malignant tumors in children and adolescents and is characterized by early metastasis. High-mobility group N (HMGN) domains are involved in the development of several tumors. Our previous study found that HMGN5 is highly expressed in osteosarcoma tissues and knockdown of HMGN5 inhibits migration and invasion of U-2 OS and Saos-2 cells. A hypoxic environment is commonly found in solid tumors such as osteosarcoma and is likely to be associated with tumor metastasis, so we further explored the relationship between HMGN5 and the hypoxic environment. Hypoxia-inducible factor 1A (HIF1A) is an adaptive factor in the hypoxic environment. We found that HIF1A and HMGN5 were upregulated in osteosarcoma (OS) cells cultured in the hypoxic environment, and the results of overexpression and knockdown experiments showed that HIF1A upregulated the transcription factor GATA1 and further promoted the expression of HMGN5. In addition, MMP2 and MMP9 were subsequently upregulated through the c-jun pathway, and finally, this promoted the migration and invasion of OS cells. It is suggested that HMGN5 may be an important downstream factor for HIF1A to promote osteosarcoma metastasis. It has an important clinical significance for the selection of therapeutic targets for osteosarcoma.

scholarly journals Functional Interaction of E1AF and Sp1 in Glioma Invasion

2007 ◽  
Vol 27 (24) ◽  
pp. 8770-8782 ◽  
Author(s):  
Jianhai Jiang ◽  
Yuanyan Wei ◽  
Jialin Shen ◽  
Dan Liu ◽  
Xiaoning Chen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Tumor Metastasis ◽  
Migration And Invasion ◽  
Functional Interaction ◽  
Glioma Invasion ◽  
Cooperative Effort ◽  
Binding Partner ◽  
Sp1 Transcription Factor ◽  
Epidermal Growth ◽  
First Time

ABSTRACT Transcription factor E1AF is widely known to play critical roles in tumor metastasis via directly binding to the promoters of genes involved in tumor migration and invasion. Here, we report for the first time E1AF as a novel binding partner for ubiquitously expressed Sp1 transcription factor. E1AF forms a complex with Sp1, contributes to Sp1 phosphorylation and transcriptional activity, and functions as a mediator between epidermal growth factor and Sp1 phosphorylation and activity. Sp1 functions as a carrier bringing E1AF to the promoter region, thus activating transcription of glioma-related gene for β1,4-galactosyltransferase V (GalT V; EC 2.4.1.38). Biologically, E1AF functions as a positive invasion regulator in glioma in cooperation with Sp1 partly via up-regulation of GalT V. This report describes a new mechanism of glioma invasion involving a cooperative effort between E1AF and Sp1 transcription factors.

scholarly journals miR-335-laden B Cell-Derived Extracellular Vesicles Promote SOX4-Dependent Apoptosis in Human Multiple Myeloma Cells

2021 ◽  
Vol 11 (12) ◽  
pp. 1240
Author(s):  
Elisabetta Lombardi ◽  
Gonzalo Almanza ◽  
Kinga Kowal ◽  
Marco Valvasori ◽  
Francesco Agostini ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Transcription Factor ◽  
Extracellular Vesicles ◽  
Plasma Cells ◽  
Cell Model ◽  
Hypoxia Inducible Factor ◽  
Tumor Development ◽  
High Mobility ◽  
Incurable Cancer ◽  
Human Multiple Myeloma

Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells in the bone marrow. Despite novel therapies, MM still remains an incurable cancer and new strategies are needed. Increased expression of the transcription factor Sex-determining region Y-related high-mobility-group box transcription factor 4 (SOX4) has been correlated with tumor development and progression through a variety of distinct processes, including inhibition of apoptosis, increased cell invasion and metastasis, and induction and maintenance of cancer-initiating cells. The role of SOX4 in MM is largely unknown. Since SOX4 is a known target of miR-335, we used miR-335 to assess whether SOX4 modulation could promote apoptosis in MM cells. Using an MM cell model we show that miR-335 acts both on SOX4-related genes (AKT, PI3K) and hypoxia-inducible factor 1-alpha (Hif1-α). In addition, we show miR-335-laden extracellular vesicles induced in B cells (iEVs) are also effective in targeting SOX4, causing apoptosis. Collectively, we propose that miR-335-laden iEVs could be developed as a novel form of gene therapy in MM.

scholarly journals Transcription Factor CTCFL Promotes Cell Proliferation, Migration, and Invasion in Gastric Cancer via Activating DPPA2

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Haibo Yao ◽  
Qinshu Shao ◽  
Yanfei Shao
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Transcription Factor ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Positive Role ◽  
Qrt Pcr ◽  
The Relationship

Objective. To explore the relationship between CTCFL and DPPA2 and validate the positive role of CTCFL/DPPA2 in cell malignant behaviors in gastric cancer. Methods. We predicted gastric cancer-related transcription factors and corresponding target mRNAs through bioinformatics. Levels of CTCFL and DPPA2 were assessed via qRT-PCR and western blot. In vitro experiments were utilized to assay the cell biological behaviors. CHIP was utilized for the assessment of the targeted relationship between CTCFL and DPPA2. Results. CTCFL and DPPA2 were both highly expressed in gastric cancer cells, and high CTCFLL and DPPA2 could promote cell malignant behaviors. CHIP validated that DPPA2 was a target of CTCFL. In addition, high DPPA2 rescued the repressive impact of CTCFL silencing on the cell proliferation, migration, and invasion in gastric cancer. Conclusion. The transcription factor CTCFL fosters cell proliferative, migratory, and invasive properties via activating DPPA2 in gastric cancer.

scholarly journals Hypoxia, endoplasmic reticulum stress and chemoresistance: dangerous liaisons

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Muhlis Akman ◽  
Dimas Carolina Belisario ◽  
Iris Chiara Salaroglio ◽  
Joanna Kopecka ◽  
Massimo Donadelli ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Endoplasmic Reticulum ◽  
Transcription Factor ◽  
Er Stress ◽  
Hypoxia Inducible Factor ◽  
Apoptosis Inhibition ◽  
Hypoxic Environment ◽  
Anti Cancer ◽  
Anti Oxidant ◽  
Resistance To Chemotherapy

AbstractSolid tumors often grow in a micro-environment characterized by < 2% O2 tension. This condition, together with the aberrant activation of specific oncogenic patwhays, increases the amount and activity of the hypoxia-inducible factor-1α (HIF-1α), a transcription factor that controls up to 200 genes involved in neoangiogenesis, metabolic rewiring, invasion and drug resistance. Hypoxia also induces endoplasmic reticulum (ER) stress, a condition that triggers cell death, if cells are irreversibly damaged, or cell survival, if the stress is mild.Hypoxia and chronic ER stress both induce chemoresistance. In this review we discuss the multiple and interconnected circuitries that link hypoxic environment, chronic ER stress and chemoresistance. We suggest that hypoxia and ER stress train and select the cells more adapted to survive in unfavorable conditions, by activating pleiotropic mechanisms including apoptosis inhibition, metabolic rewiring, anti-oxidant defences, drugs efflux. This adaptative process unequivocally expands clones that acquire resistance to chemotherapy.We believe that pharmacological inhibitors of HIF-1α and modulators of ER stress, although characterized by low specificty and anti-cancer efficacy when used as single agents, may be repurposed as chemosensitizers against hypoxic and chemorefractory tumors in the next future.

scholarly journals Long Noncoding RNA WDFY3-AS2 Represses the Progression of Esophageal Cancer through miR-18a/PTEN Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Qingling Kong ◽  
Guangcai Li ◽  
Gang Yin ◽  
Kun Li ◽  
Dongqing Zhang ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
Regulatory Mechanism ◽  
Malignant Tumors ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
The Relationship ◽  
Competitive Endogenous Rna

Background. Understanding the role of lncRNAs in the development of human malignancies is necessary for the targeted therapy of malignant tumors, including esophageal cancer (EC). Nevertheless, the specific role and regulatory mechanism of lncRNA WDFY3-AS2 in EC are still unclear. Here, we examined the functional role and regulatory mechanism of WDFY3-AS2 in EC. Materials and Methods. RT-qPCR assay was applied to measure the expression of WDFY3-AS2 and miR-18a in EC samples and cells. The luciferase reporter and RIP assays were used to check the relationship between WDFY3-AS2, miR-18a, and PTEN. Counting Clock Kit-8 (CCK-8) assay was carried out to detect cell viability, and transwell assays were used for measuring cell migration and invasion. Results. Underexpression of WDFY3-AS2 was found in EC specimens and cells, which predicted a poor prognosis of EC patients. Reexpression of WDFY3-AS2 repressed the progression of EC via inhibiting cell proliferation, migration, and invasion. Additionally, WDFY3-AS2 was negatively correlated with miR-18a and positively with PTEN. Furthermore, we discovered that the expression of PTEN decreased by miR-18a mimic was rescued by WDFY3-AS2 overexpression. Conclusions. WDFY3-AS2 modulates the expressional level of PTEN as a competitive endogenous RNA via sponging miR-18a in EC, which suggests that the WDFY3-AS2/miR-18a/PTEN pathway might be involved in the progression of EC.

IMPROVEMENT OF SPRING DURUM WHEAT SELECTION METHODOLOGIES UNDER CLIMATE CHANGE CONDITIONS

1970 ◽  
pp. 33-36
Author(s):  
А. I. Grabovets ◽  
V. P. Kadushkina ◽  
S. А. Kovalenko
Keyword(s):  
Grain Yield ◽  
Durum Wheat ◽  
Correlation Coefficient ◽  
Harvest Index ◽  
Unit Area ◽  
Correlation Coefficients ◽  
Chemical Mutagenesis ◽  
Main Method ◽  
The Relationship ◽  
Selection Of

With the growing aridity of the climate on the Don, it became necessary to improve the methodology for conducting the  breeding of spring durum wheat. The main method of obtaining the source material remains intraspecific step hybridization. Crossings were performed between genetically distant forms, differing in origin and required traits and properties. The use of chemical mutagenesis was a productive way to change the heredity of genotypes in terms of drought tolerance. When breeding for productivity, both in dry years of research and in favorable years, the most objective markers were identified — the size of the aerial mass, the mass of grain per plant, spike, and harvest index. The magnitude of the correlation coefficients between the yield per unit area and the elements of its structure is established. It was most closely associated with them in dry years, while in wet years it decreased. Power the correlation of the characteristics of the pair - the grain yield per square meter - the aboveground biomass averaged r = 0.73, and in dry years it was higher (0.91) than in favorable ones (0.61 - 0.70) , between the harvest and the harvest index - r = 0.81 (on average). In dry years, the correlation coefficient increased to 0.92. Research data confirms the greatest importance of the mass of grain from one ear and the plant in the formation of grain yield per unit area in both dry and wet years. In dry years, the correlation coefficient between yield and grain mass per plant was on average r = 0.80; in favorable years, r = 0.69. The relationship between yield and grain mass from the ear was greater — r = 0.84 and r = 0.82, respectively. Consequently, the breeding significance of the aboveground mass and the productivity of the ear, as a criterion for the selection of the crop, especially increases in the dry years. They were basic in the selection.

Analisa Pemilihan Moda Transportasi Umum Rute Tanjung Karang – Bandara Radin Inten II Dengan Stated Preference dan Uji Crame’s V

2018 ◽  
Vol 2 (2) ◽  
pp. 137
Author(s):  
Muhammad Abi Berkah Nadi
Keyword(s):  
Regression Analysis ◽  
Utility Function ◽  
Stated Preference ◽  
Technical Analysis ◽  
Chi Square ◽  
Time Headway ◽  
Independent Variable ◽  
The Relationship ◽  
Selection Of

Radin Inten II Airport is a national flight in Lampung Province. In this study using the technical analysis stated preference which is the approach by conveying the choice statement in the form of hypotheses to be assessed by the respondent. By using these techniques the researcher can fully control the hypothesized factors. To determine utility function for model forecasting in fulfilling request of traveler is used regression analysis with SPSS program. The analysis results obtained that the passengers of the dominant airport in the selection of modes of cost attributes than on other attributes. From the result of regression analysis, the influence of independent variable to the highest dependent variable is when the five attributes are used together with the R square value of 8.8%. The relationship between cost, time, headway, time acces and service with the selection of modes, the provision that states whether or not there is a decision. The significance of α = 0.05 with chi-square. And the result of Crame's V test average of 0.298 is around the middle, then the relationship is moderate enough.

Anticancer Activity of Natural Flavonoids: Inhibition of HIF-1α Signaling Pathway

2020 ◽  
Vol 23 (26) ◽  
pp. 2945-2959 ◽  
Author(s):  
Xiangping Deng ◽  
Yijiao Peng ◽  
Jingduo Zhao ◽  
Xiaoyong Lei ◽  
Xing Zheng ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Secondary Metabolites ◽  
Anticancer Agents ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Pharmacological Activities ◽  
Hypoxia Inducible Factor 1 ◽  
The Past ◽  
Low Toxicity ◽  
Tumor Blood Vessels

Rapid tumor growth is dependent on the capability of tumor blood vessels and glycolysis to provide oxygen and nutrients. Tumor hypoxia is a common characteristic of many solid tumors, and it essentially happens when the growth of the tumor exceeds the concomitant angiogenesis. Hypoxia-inducible factor 1 (HIF-1) as the critical transcription factor in hypoxia regulation is activated to adapt to this hypoxia situation. Flavonoids, widely distributed in plants, comprise many polyphenolic secondary metabolites, possessing broadspectrum pharmacological activities, including their potentiality as anticancer agents. Due to their low toxicity, intense efforts have been made for investigating natural flavonoids and their derivatives that can be used as HIF-1α inhibitors for cancer therapy during the past few decades. In this review, we sum up the findings concerning the inhibition of HIF-1α by natural flavonoids in the last few years and propose the idea of designing tumor vascular and glycolytic multi-target inhibitors with HIF-1α as one of the targets.

A Biomarker Combining Imaging and Neuropsychological Assessment for Tracking Early Alzheimer's Disease in Clinical Trials

2018 ◽  
Vol 15 (5) ◽  
pp. 429-442 ◽  
Author(s):  
Nishant Verma ◽  
S. Natasha Beretvas ◽  
Belen Pascual ◽  
Joseph C. Masdeu ◽  
Mia K. Markey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Latent Variable ◽  
Brain Regions ◽  
Disease Assessment ◽  
Latent Variable Analysis ◽  
The Relationship ◽  
Selection Of

Background: Combining optimized cognitive (Alzheimer's Disease Assessment Scale- Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer's disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer's disease. Method: Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers. Results: Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8±4.9% specificity at 80% sensitivity) that will evolve to Alzheimer's disease for clinical trials. Conclusion: The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer’s disease.

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