scholarly journals The genotypic and phenotypic impact of hypoxia microenvironment on glioblastoma cell lines

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lucy Wanjiku Macharia ◽  
Wanjiru Muriithi ◽  
Carlos Pilotto Heming ◽  
Dennis Kirii Nyaga ◽  
Veronica Aran ◽  
...  
Keyword(s):  
Cell Lines ◽  
Patient Survival ◽  
Morphological Changes ◽  
Tumour Microenvironment ◽  
Cell Phenotype ◽  
Hypoxia Inducible Factors ◽  
Glut 1 ◽  
Adaptation Mechanisms ◽  
Poor Patient ◽  
Poor Patient Survival

Abstract Background Glioblastoma is a fatal brain tumour with a poor patient survival outcome. Hypoxia has been shown to reprogram cells towards a stem cell phenotype associated with self-renewal and drug resistance properties. Activation of hypoxia-inducible factors (HIFs) helps in cellular adaptation mechanisms under hypoxia. Similarly, miRNAs are known to be dysregulated in GBM have been shown to act as critical mediators of the hypoxic response and to regulate key processes involved in tumorigenesis. Methods Glioblastoma (GBM) cells were exposed to oxygen deprivation to mimic a tumour microenvironment and different cell aspects were analysed such as morphological changes and gene expression of miRNAs and survival genes known to be associated with tumorigenesis. Results It was observed that miR-128a-3p, miR-34-5p, miR-181a/b/c, were down-regulated in 6 GBM cell lines while miR-17-5p and miR-221-3p were upregulated when compared to a non-GBM control. When the same GBM cell lines were cultured under hypoxic microenvironment, a further 4–10-fold downregulation was observed for miR-34-5p, miR-128a-3p and 181a/b/c while a 3–6-fold upregulation was observed for miR-221-3p and 17-5p for most of the cells. Furthermore, there was an increased expression of SOX2 and Oct4, GLUT-1, VEGF, Bcl-2 and survivin, which are associated with a stem-like state, increased metabolism, altered angiogenesis and apoptotic escape, respectively. Conclusion This study shows that by mimicking a tumour microenvironment, miRNAs are dysregulated, stemness factors are induced and alteration of the survival genes necessary for the cells to adapt to the micro-environmental factors occurs. Collectively, these results might contribute to GBM aggressiveness.

scholarly journals PD-1 expression on uveal melanoma induces tumor proliferation and predicts poor patient survival

2020 ◽  
Vol 35 (3) ◽  
pp. 50-58
Author(s):  
Zhongming Jiang ◽  
Yuexiang Yan ◽  
Juan Dong ◽  
Lingling Duan
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Cell Lines ◽  
Uveal Melanoma ◽  
Patient Survival ◽  
Malignant Tumors ◽  
Tumor Diameter ◽  
Tumor Cell Proliferation ◽  
Poor Patient ◽  
Poor Patient Survival

Introduction: Uveal melanoma is one of the most common primary intraocular malignant tumors with poor prognosis and limited treatments. Programmed cell death receptor-1 (PD-1) blockade represents the primary treatment strategy of immune checkpoint inhibition; however, there is a lack of studies on whether PD-1 expression in primary (ocular) uveal melanoma affects tumor progression. Methods: PD-1 expression in 82 cases of primary (ocular) uveal melanoma was detected by immunohistochemistry. The clinical significance of PD-1 expression was evaluated using univariate and multivariate analysis. PD-1 overexpression and knockdown studies were conducted in C918 and Mum-2B cell lines to analyze the effect of PD-1 expression on tumor cell proliferation and intracellular cell signaling transduction. real-time qPCR (RT-qPCR) and western blot analysis were performed to investigate the gene expression level. CCK8 assays were performed to examine the cell proliferation ability. Results: High expression of primary (ocular) intratumor PD-1 was associated with poor patient survival. Moreover, PD-1 expression was correlated with the largest tumor diameter. PD-1 expression and optic nerve invasion were independent prognostic risk factors. PD-1 overexpression in uveal melanoma cell lines promoted tumor cell proliferation, while knockdown of PD-1 inhibited cell proliferation capacity. Conclusion: Our study established the role of PD-1 in the progression of uveal melanoma and provided a new potential treatment selection for uveal melanoma.

scholarly journals Stomatin-like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Fei Sun ◽  
Wen Ding ◽  
Jie-Hua He ◽  
Xiao-Jing Wang ◽  
Ze-Biao Ma ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Patient Survival ◽  
Poor Patient ◽  
Poor Patient Survival

scholarly journals Elevated expression of SATB1 is involved in pancreatic tumorigenesis and is associated with poor patient survival

2017 ◽  
Vol 16 (6) ◽  
pp. 8842-8848 ◽  
Author(s):  
Lei Guo ◽  
Jianjiang Zheng ◽  
Tao Yu ◽  
Yuequan Liu ◽  
Lukun Duo
Keyword(s):  
Patient Survival ◽  
Poor Patient ◽  
Elevated Expression ◽  
Poor Patient Survival

Regulation of the breast cancer stem cell phenotype by hypoxia-inducible factors

2015 ◽  
Vol 129 (12) ◽  
pp. 1037-1045 ◽  
Author(s):  
Gregg L. Semenza
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Primary Tumour ◽  
Tumour Microenvironment ◽  
Cell Phenotype ◽  
Breast Cancer Patients ◽  
Hypoxia Inducible Factors ◽  
Cancer Stem Cell Phenotype ◽  
Response To Chemotherapy ◽  
Small Subpopulation

The small subpopulation of breast cancer cells that possess the capability for self-renewal and formation of secondary tumours that recapitulate the heterogeneity of the primary tumour are referred to as tumour-initiating cells or BCSCs (breast cancer stem cells). The hypoxic tumour microenvironment and chemotherapy actively induce the BCSC phenotype. HIFs (hypoxia-inducible factors) are required and molecular mechanisms by which they promote the BCSC phenotype have recently been delineated. HIF inhibitors block chemotherapy-induced enrichment of BCSCs, suggesting that their use may improve the response to chemotherapy and increase the survival of breast cancer patients.

Lamins as cancer biomarkers

2010 ◽  
Vol 38 (1) ◽  
pp. 297-300 ◽  
Author(s):  
Clare R. Foster ◽  
Stefan A. Przyborski ◽  
Robert G. Wilson ◽  
Christopher J. Hutchison
Keyword(s):  
Cancer Cells ◽  
Patient Survival ◽  
Cancer Biomarkers ◽  
Tumour Cells ◽  
Diagnostic Biomarkers ◽  
Cancer Subtypes ◽  
Multifunctional Proteins ◽  
Poor Patient ◽  
Poor Patient Survival

Lamins are multifunctional proteins that are often aberrantly expressed or localized in tumours. Here, we endeavour to assess their uses as cancer biomarkers: to diagnose tumours, analyse cancer characteristics and predict patient survival. It appears that the nature of lamin function in cancer is very complex. Lamin expression can be variable between and even within cancer subtypes, which limits their uses as diagnostic biomarkers. Expression of A-type lamins is a marker of differentiated tumour cells and has been shown to be a marker of good or poor patient survival depending on tumour subtype. Further research into the functions of lamins in cancer cells and the mechanisms that determine its patterns of expression may provide more potential uses of lamins as cancer biomarkers.

scholarly journals The U2AF2 /circRNA ARF1/miR-342–3p/ISL2 feedback loop regulates angiogenesis in glioma stem cells

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Yang Jiang ◽  
Jinpeng Zhou ◽  
Junshuang Zhao ◽  
Haiying Zhang ◽  
Long Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Development ◽  
Feedback Loop ◽  
Rna Binding ◽  
Patient Survival ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Glioma Stem Cells ◽  
Poor Patient ◽  
Poor Patient Survival

Abstract Background Glioma is the most common and lethal primary brain tumor in adults, and angiogenesis is one of the key factors contributing to its proliferation, aggressiveness, and malignant transformation. However, the discovery of novel oncogenes and the study of its molecular regulating mechanism based on circular RNAs (circRNAs) may provide a promising treatment target in glioma. Methods Bioinformatics analysis, qPCR, western blotting, and immunohistochemistry were used to detect the expression levels of ISL2, miR-342–3p, circRNA ARF1 (cARF1), U2AF2, and VEGFA. Patient-derived glioma stem cells (GSCs) were established for the molecular experiments. Lentiviral-based infection was used to regulate the expression of these molecules in GSCs. The MTS, EDU, Transwell, and tube formation assays were used to detect the proliferation, invasion, and angiogenesis of human brain microvessel endothelial cells (hBMECs). RNA-binding protein immunoprecipitation, RNA pull-down, dual-luciferase reporter, and chromatin immunoprecipitation assays were used to detect the direct regulation mechanisms among these molecules. Results We first identified a novel transcription factor related to neural development. ISL2 was overexpressed in glioma and correlated with poor patient survival. ISL2 transcriptionally regulated VEGFA expression in GSCs and promoted the proliferation, invasion, and angiogenesis of hBMECs via VEGFA-mediated ERK signaling. Regarding its mechanism of action, cARF1 upregulated ISL2 expression in GSCs via miR-342–3p sponging. Furthermore, U2AF2 bound to and promoted the stability and expression of cARF1, while ISL2 induced the expression of U2AF2, which formed a feedback loop in GSCs. We also showed that both U2AF2 and cARF1 had an oncogenic effect, were overexpressed in glioma, and correlated with poor patient survival. Conclusions Our study identified a novel feedback loop among U2AF2, cARF1, miR-342–3p, and ISL2 in GSCs. This feedback loop promoted glioma angiogenesis, and could provide an effective biomarker for glioma diagnosis and prognostic evaluation, as well as possibly being used for targeted therapy.

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