scholarly journals A Candidate Prognostic Biomarker Complement Factor I Promotes Malignant Progression in Glioma

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaomin Cai ◽  
Wenjin Qiu ◽  
Mengshu Qian ◽  
Shuang Feng ◽  
Chenghao Peng ◽  
...  
Keyword(s):  
Glioma Cell ◽  
Prognostic Biomarker ◽  
Malignant Progression ◽  
Migration And Invasion ◽  
Complement Factor ◽  
Factor I ◽  
Complement Factor I ◽  
Genome Atlas

Objectives: Glioma is the most common and aggressive type of primary central nervous system (CNS) tumor in adults and is associated with substantial mortality rates. The aim of our study was to evaluate the prognostic significance and function of the complement factor I (CFI) in glioma.Materials and Methods: The expression levels of CFI in glioma tissues and the survival of the CFIhigh and CFIlow patient groups were analyzed using The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx). The correlation between CFI expression and clinicopathological features of glioma was determined by univariate and multivariate Cox regression analyses in the Chinese Glioma Genome Atlas (CGGA) database. The functional role of CFI in glioma was established through routine in vitro and in vivo assays.Results: CFI is overexpressed in glioma and its high levels correlated with poor outcomes in both TCGA and CGGA datasets. Furthermore, CFI was identified as an independent prognostic factor of glioma in the CGGA database. CFI knockdown in glioma cell lines inhibited growth in vitro and in vivo, whereas its ectopic expression increased glioma cell proliferation, migration, and invasion in vitro. CFI protein levels were also significantly higher in the glioma tissues resected from patients and correlated to worse prognosis.Conclusions: CFI is a potential prognostic biomarker in glioma and drives malignant progression.

scholarly journals Functional expression of complement factor I following AAV-mediated gene delivery in the retina of mice and human cells

Gene Therapy ◽  
2021 ◽  
Author(s):  
Anna K. Dreismann ◽  
Michelle E. McClements ◽  
Alun R. Barnard ◽  
Elise Orhan ◽  
Jane P. Hughes ◽  
...  
Keyword(s):  
Complement System ◽  
Functional Expression ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Complement Factor ◽  
Factor I ◽  
Complement Factor I ◽  
Age Related ◽  
The Complement System

AbstractDry age-related macular degeneration (AMD) is characterised by loss of central vision and currently has no approved medical treatment. Dysregulation of the complement system is thought to play an important role in disease pathology and supplementation of Complement Factor I (CFI), a key regulator of the complement system, has the potential to provide a treatment option for AMD. In this study, we demonstrate the generation of AAV constructs carrying the human CFI sequence and expression of CFI in cell lines and in the retina of C57BL/6 J mice. Four codon optimised constructs were compared to the most common human CFI sequence. All constructs expressed CFI protein; however, most codon optimised sequences resulted in significantly reduced CFI secretion compared to the non-optimised CFI sequence. In vivo expression analysis showed that CFI was predominantly expressed in the RPE and photoreceptors. Secreted protein in vitreous humour was demonstrated to be functionally active. The findings presented here have led to the formulation of an AAV-vectored gene therapy product currently being tested in a first-in-human clinical trial in subjects with geographic atrophy secondary to dry AMD (NCT03846193).

scholarly journals circATP2A2 promotes osteosarcoma progression by upregulating MYH9

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 1749-1761
Author(s):  
Xin Cao ◽  
Xianfeng Meng ◽  
Peng Fu ◽  
Lin Wu ◽  
Zhen Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Area Under Curve ◽  
Prognostic Biomarker ◽  
Migration And Invasion ◽  
Promising Target ◽  
Repressive Effect ◽  
Cell Malignancy

Abstract Osteosarcoma (OS) is a highly metastatic primary malignant tumor. CircRNA hsa_circ_0028173 (circATP2A2) has been uncovered to be related to the advancement of OS. However, the biological role of circATP2A2 in OS has not been validated. circATP2A2 and MYH9 were upregulated while miR-335-5p was downregulated in OS. OS patients with high circATP2A2 expression displayed a shorter overall survival and the area under curve of circATP2A2 was 0.77, manifesting that circATP2A2 might be a diagnostic and prognostic biomarker. circATP2A2 silencing repressed OS cell proliferation and glycolysis in vivo and constrained OS cell proliferation, glycolysis, migration, and invasion in vitro. circATP2A2 regulated MYH9 expression through sponging miR-335-5p. MiR-335-5p inhibitor reversed the repressive effect of circATP2A2 knockdown on OS cell malignancy and glycolysis. MYH9 overexpression overturned miR-335-5p upregulation-mediated OS cell malignancy and glycolysis. circATP2A2 accelerated OS cell malignancy and glycolysis through upregulating MYH9 via sponging miR-335-5p, offering a promising target for OS treatment.

scholarly journals Curcumol inhibits malignant biological behaviors and TMZ-resistance of glioma cells via reducing long noncoding RNA FoxD2-As1 promoted EZH2 activation

2021 ◽  
Author(s):  
Xuyang Lv ◽  
Jiangchuan Sun ◽  
Linfeng Hu ◽  
Ying Qian ◽  
Chunlei Fan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Noncoding Rna ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Self Renewal

Abstract Background: Although curcumol has been shown to possess antitumor effects in several cancers, its effects on glioma are largely unknown. Recently, lncRNAs have been reported to play an oncogenic role through epigenetic modifications. Therefore, here, we investigated whether curcumol inhibited glioma progression by reducing FOXD2-AS1-mediated enhancer of zeste homolog 2 (EZH2) activation.Methods: MTT, colony formation, flow cytometry, Transwell, and neurosphere formation assays were used to assess cell proliferation, cell cycle, apoptosis, the percentage of CD133+ cells, the migration and invasion abilities, and the self-renewal ability. qRT-PCR, western blotting, immunofluorescence, and immunohistochemical staining were used to detect mRNA and protein levels. Isobologram analysis and methylation-specific PCR were used to analyze the effects of curcumol on TMZ resistance in glioma cells. DNA pull-down and Chip assays were employed to explore the molecular mechanism underlying the functions of curcumol in glioma cells. Tumorigenicity was determined using a xenograft formation assay. Results: Curcumol inhibited the proliferation, metastasis, self-renewal ability, and TMZ resistance of glioma cells in vitro and in vivo. FOXD2-AS1 was highly expressed in glioma cell lines, and its expression was suppressed by curcumol treatment in a dose- and time-dependent manner. The forced expression of FOXD2-AS1 abrogated the effect of curcumol on glioma cell proliferation, metastasis, self-renewal ability, and TMZ resistance. Moreover, the forced expression of FOXD2-AS1 reversed the inhibitory effect of curcumol on EZH2 activation.Conclusions: We showed for the first time that curcumol is effective in inhibiting malignant biological behaviors and TMZ-resistance of glioma cells by suppressing FOXD2-AS1-mediated EZH2 activation on anti-oncogenes. Our findings offer the possibility of exploiting curcumol as a promising therapeutic agent for glioma treatment and may provide an option for the clinical application of this natural herbal medicine.

scholarly journals LncRNA FOXD3-AS1 Promotes the Malignant Progression of Nasopharyngeal Carcinoma Through Enhancing the Transcription of YBX1 by H3K27Ac Modification

2021 ◽  
Vol 11 ◽  
Author(s):  
Huiyun Yang ◽  
Yuliang Pan ◽  
Jun Zhang ◽  
Long Jin ◽  
Xi Zhang
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Bioinformatics Analysis ◽  
Protein Translation ◽  
Malignant Progression ◽  
Migration And Invasion ◽  
Mouse Tumor ◽  
Rna Immunoprecipitation ◽  
Tumor Growth And Metastasis

BackgroundLong noncoding RNAs (lncRNAs) can affect the progression of various tumors, including nasopharyngeal carcinoma (NPC). Here, lncRNA FOXD3-AS1 is highly expressed in NPC tissues through bioinformatics analysis and related to the malignant progression of NPC.MethodsBioinformatics analysis and real-time reverse transcription quantitative PCR(RT-qPCR) assay were applied to identify the expression of FOXD3-AS1 in NPC tissues and cells. Specific short hairpin RNAs (shRNAs) or overexpression plasmids were used to knockdown or upregulate FOXD3-AS1 in NPC cells. The effect of FOXD3-AS1 on proliferation and metastasis of NPC was confirmed by CCK8, colony formation, transwell assays in vitro and mouse tumor growth and metastasis models in vivo, of which the mechanism was explored by RNA pull down, mass spectrometry (MS), RNA Immunoprecipitation (RIP), chromatin immunoprecipitation (CHIP) and luciferase assays.ResultsFOXD3-AS1 was highly expressed in NPC tissues and cells. Knockdown of FOXD3-AS1 significantly inhibited proliferation, migration, and invasion of NPC cells in vitro and vivo. FOXD3-AS1 could specifically bind to YBX1 and have a positive effect on the expression of YBX1. Bioinformatics analysis showed that the promoter of YBX1 had a high enrichment of H3K27ac, which promote mRNA transcription and protein translation of YBX1. Moreover, overexpression of YBX1 could reverse the proliferation, migration and invasion arrest caused by FOXD3-AS1 knockdown.ConclusionLncRNA FOXD3-AS1 is highly expressed and promotes malignant phenotype in NPC, which may provide a new molecular mechanism for NPC.

scholarly journals Amlexanox Enhances Temozolomide-Induced Anti-Tumor Effects In Human Glioblastoma Cells By Inhibiting Ikbke And The Akt-mtor Signaling Pathway

2020 ◽  
Author(s):  
Jinbiao Xiong ◽  
Gaochao Guo ◽  
Lianmei Guo ◽  
Zengguang Wang ◽  
Zhijuan Chen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Viability ◽  
Glioma Cell ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Migration And Invasion ◽  
Cell Viability Assay ◽  
Primary Glioma

Abstract Background: Temozolomide (TMZ), as the first-line chemotherapeutic agent for the treatment of glioblastoma multiforme (GBM), often fails to improve the prognosis of GBM patients due to the quick development of resistance. The need for more effective management of GBM is urgent. The aim of this study is to evaluate the efficacy of combined therapy with TMZ and amlexanox, a selective inhibitor of inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE), for GBM.Methods: in vitro, cell viability assay, apoptosis analysis, western blot, migration and invasion assay were used. In vivo, intracranial tumor models were constructed and the immunohistochemistry were used. Results: We found that combined treatment resulted in significant induction of cellular apoptosis and the inhibition of cell viability, migration and invasion in primary glioma cell and in the human glioma cell line, U87 MG. TMZ enhanced expression of phosphoration of adenosine 5‘-monophosphate-activated protein kinase (p-AMPK) and amlexanox led to reduction of IKBKE, with no impact on p-AMPK. Furthermore, we demonstrated that, compared to other groups treated with each component alone, TMZ combined with amlexanox effectively inhibited phosphorylation of protein kinase B (AKT) and mammalian target of rapamycin (mTOR). In addition, the combination treatment also clearly reduced in vivo tumor volume and prolonged median survival time in the xenograft mouse model. Conclusion: These results suggest that amlexanox sensitized primary glioma cell and U87 MG cell to TMZ at least partially though the suppression of IKBKE activation and the attenuation of AKT activation. Overall, combined treatment with TMZ and amlexanox may provide a promising possibility for improving the prognosis of glioblastoma patients in clinical practice.

scholarly journals Curcumol inhibits malignant biological behaviors and TMZ-resistance of glioma cells via reducing long noncoding RNA FoxD2-As1 promoted EZH2 activation

2021 ◽  
Author(s):  
Xuyang Lv ◽  
Jiangchuan Sun ◽  
Linfeng Hu ◽  
Ying Qian ◽  
Chunlei Fan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Noncoding Rna ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Self Renewal

Abstract Background: Although curcumol has been shown to possess antitumor effects in several cancers, its effects on glioma are largely unknown. Recently, lncRNAs have been reported to play an oncogenic role through epigenetic modifications. Therefore, here, we investigated whether curcumol inhibited glioma progression by reducing FOXD2-AS1-mediated enhancer of zeste homolog 2 (EZH2) activation.Methods: MTT, colony formation, flow cytometry, Transwell, and neurosphere formation assays were used to assess cell proliferation, cell cycle, apoptosis, the percentage of CD133+ cells, the migration and invasion abilities, and the self-renewal ability. qRT-PCR, western blotting, immunofluorescence, and immunohistochemical staining were used to detect mRNA and protein levels. Isobologram analysis and methylation-specific PCR were used to analyze the effects of curcumol on TMZ resistance in glioma cells. DNA pull-down and Chip assays were employed to explore the molecular mechanism underlying the functions of curcumol in glioma cells. Tumorigenicity was determined using a xenograft formation assay. Results: Curcumol inhibited the proliferation, metastasis, self-renewal ability, and TMZ resistance of glioma cells in vitro and in vivo. FOXD2-AS1 was highly expressed in glioma cell lines, and its expression was suppressed by curcumol treatment in a dose- and time-dependent manner. The forced expression of FOXD2-AS1 abrogated the effect of curcumol on glioma cell proliferation, metastasis, self-renewal ability, and TMZ resistance. Moreover, the forced expression of FOXD2-AS1 reversed the inhibitory effect of curcumol on EZH2 activation.Conclusions: We showed for the first time that curcumol is effective in inhibiting malignant biological behaviors and TMZ-resistance of glioma cells by suppressing FOXD2-AS1-mediated EZH2 activation on anti-oncogenes. Our findings offer the possibility of exploiting curcumol as a promising therapeutic agent for glioma treatment and may provide an option for the clinical application of this natural herbal medicine.

In vitro biosynthesis of complement factor I by human endothelial cells

1992 ◽  
Vol 22 (1) ◽  
pp. 213-217 ◽  
Author(s):  
Nathalie Julen ◽  
HÉLÈNe Dauchel ◽  
Claudie Lemercier ◽  
Robert B. Sim ◽  
Marc Fontaine ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Complement Factor ◽  
Human Endothelial Cells ◽  
Factor I ◽  
Complement Factor I ◽  
In Vitro Biosynthesis

scholarly journals miR-517a is up-regulated in glioma and promotes glioma tumorigenesis in vitro and in vivo

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Cheng-li Du ◽  
Fei Peng ◽  
Ke-qin Liu
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Migration And Invasion ◽  
Functional Assay ◽  
Normal Brain ◽  
Pathology Classification ◽  
The Status ◽  
Induced Apoptosis

Abstract miR-517a has been reported to act as an oncogenic miRNA in human hepatocellular carcinoma and lung cancer. However, the roles and underlying molecular mechanism of miR-517a in glioma remain unclear. In the present study, the expression of miR-517a in clinical glioma tissues and glioma cell lines was examined by quantitative real-time PCR (qRT-PCR). Transfected with knockdown or forced expression of miR-517a, the effects of miR-517a on cell proliferation, migration, and invasion were detected through in vitro and in vivo tumorigenesis assays. Here, we report that miR-517a expression was up-regulated in glioma tissues when compared with normal brain tissues, and up-regulation of miR-517a level is tightly correlated with the status of pathology classification of glioma. A functional assay found that overexpression of miR-517a in glioma cells markedly promoted or suppressed cell proliferation, colony formation, migration and invasion, respectively. Moreover, we revealed that the knockdown of miR-517a dramatically suppressed glioma cell growth, migration, and invasion in vitro and in vivo. Furthermore, we found that knockdown of miR-517a significantly induced apoptosis. Therefore, miR–517a acts an oncogenic miRNA that promotes tumor progression in glioma, and thus may become a promising therapeutic candidate for glioma.

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