scholarly journals The Inhibition of miR-144-3p on Cell Proliferation and Metastasis by Targeting TOP2A in HCMV-Positive Glioblastoma Cells

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3259 ◽  
Author(s):  
Jingyi Song ◽  
Qingxia Ma ◽  
Ming Hu ◽  
Dongmeng Qian ◽  
Bin Wang ◽  
...  
Keyword(s):  
Hcmv Infection ◽  
Glioma Cells ◽  
Common Type ◽  
High Recurrence Rate ◽  
Bioinformatics Analyses ◽  
The Central Nervous System ◽  
Proliferation And Metastasis ◽  
Cell Proliferation And Metastasis

Glioblastoma (GBM), the most common type of primary tumor in the central nervous system, is a very aggressive brain tumor with poor prognosis and a high recurrence rate. Increasing evidence suggests that human cytomegalovirus (HCMV) infection is related to GBM and leads to GBM cell growth and metastasis. MicroRNAs are important regulators in the growth and metastasis of glioblastoma. This study aimed to demonstrate the role of miR-144-3p in HCMV-positive glioblastoma. We found that, after HCMV infection, the expression of miR-144-3p decreased, whereas the expression of TOP2A increased. Bioinformatics analyses indicated that miR-144-3p directly targets the TOP2A 3′-UTR (Untranslated Region). We discovered that the overexpression of miR-144-3p downregulated the overexpression of TOP2A and inhibited the proliferation, clone formation, and invasion of HCMV-positive glioma in vitro. Taken together, these results show that miR-144-3p inhibited growth and promoted apoptosis in glioma cells by targeting TOP2A.

Induction of prostaglandin E2 synthesis and microsomal prostaglandin E synthase–1 expression in murine microglia by glioma-derived soluble factors

2008 ◽  
Vol 108 (2) ◽  
pp. 311-319 ◽  
Author(s):  
Yoshiteru Nakano ◽  
Etsushi Kuroda ◽  
Tomohiro Kito ◽  
Satoshi Uematsu ◽  
Shizuo Akira ◽  
...  
Keyword(s):  
Glioma Cells ◽  
Peritoneal Macrophages ◽  
Prostaglandin E ◽  
Soluble Factors ◽  
Arachidonate Cascade ◽  
Cox Inhibitor ◽  
Murine Microglia ◽  
The Central Nervous System

Object Microglia are one of the members of monocyte/macrophage lineage in the central nervous system (CNS) and exist as ramified microglia in a normal resting state, but they are activated by various stimuli, such as tumors. Activated microglia induce immune responses in the CNS, but the precise functions of microglia in glioma microenvironments are not clear. It has been reported that glioma cells produce prostaglandin (PG)E2, which promotes the growth of tumor cells and possesses immunosuppressive activity. The authors previously reported that PGE2 production by peritoneal macrophages was enhanced by glioma-derived soluble factors, which induce an immunosuppressive state. In this study, they investigated PGE2 production by microglia treated with glioma cells and assessed the role of microglia in glioma microenvironments in the mouse. Methods Microglia and peritoneal macrophages were cultured in vitro with or without lipopolysaccharide, and tumor necrosis factor (TNF) and PGE2 in the culture supernatant were measured using L929 bioassay and enzyme immunoassay. The expression of mRNA was measured using reverse transcriptase polymerase chain reaction, and the protein expression was assayed with Western blotting. In some experiments glioma cells and conditioned glioma medium were added to the microglia cultures. Results Glioma cells studied in this report did not produce a significant amount of PGE2. However, the coculture of microglia with glioma cells or conditioned glioma medium led to the production of a large amount of PGE2. The enhancement of PGE2 production by microglia was more significant than that by peritoneal macrophages. The expression of cyclooxygenase (COX)–2 and particularly the expression of microsomal PGE synthase (mPGES)–1 (a terminal enzyme of the arachidonate cascade) in microglia were enhanced by conditioned glioma medium. The enhancement of mPGES-1 expression in microglia was more significant than that in peritoneal macrophages. The production of TNF was suppressed when culturing microglia with conditioned glioma medium, but this suppression was abrogated by the addition of a COX inhibitor (NS-398) and a PGE2 receptor (EP4) antagonist. Furthermore, TNF production was not suppressed in microglia from mPGES-1–deficient mice. Conclusions These results indicate that PGE2 production by microglia is enhanced by conditioned glioma medium, which induces an immunosuppressive state in the CNS. Therefore, the manipulation of microglia, from the standpoint of PGE2, provides investigators with an important strategy to induce an effective antiglioma immune response.

scholarly journals MiR-124-3p/ZC3H15 Regulates Gastric Cancer Progression by Blocking FBXW7 Mediated Degradation of c-Myc

2020 ◽  
Author(s):  
Jianbing Hou ◽  
Yudong Liu ◽  
Du Yan ◽  
Pan Huang ◽  
Zhongze Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Biological Role ◽  
Potential Biomarker ◽  
Proliferation And Metastasis ◽  
Gastric Cancer Progression ◽  
Cell Proliferation And Metastasis

Abstract BACKGROUND: Zinc finger CCCH-type containing 15 (ZC3H15), a highly conserved eukaryotic protein, was involved in tumorigenesis and may be a potential biomarker in hepatocellular carcinoma (HCC) and acute myeloid leukemia (AML). However, the biological role of ZC3H15 in gastric cancer (GC) is unclear.METHODS: The potential correlation between ZC3H15 expression and GC prognosis was assessed based on the patient data analysis. The biological role of ZC3H15 in regulating cell proliferation and metastasis was evaluated in vitro and in vivo. In addition, the potential mechanism of ZC3H15 was investigated. RESULTS: we found that ZC3H15 expression was positively correlated with GC progression, including cell growth, metastasis and cancerogenesis. Through further investigations, we found that ZC3H15 could modulate c-Myc protein stability via suppressing the transcription of FBXW7, which was mainly responsible for c-Myc degradation. In addition, we revealed that miR-124-3p, a tumor suppressor of GC, was negatively associated with ZC3H15. We revealed that miR-124-3p was a critical upstream modulator of ZC3H15 in GC.CONCLUSIONS: Taken together, our studies unearth the important roles of ZC3H15 in GC development and suggest that miR-124-3p/ZC3H15/c-Myc axis may be a potential target for the treatment of GC.

Accumulation of AGO2 facilitates tumor proliferation and metastasis through upregulating Survivin, Vimentin and Snail in human hepatocellular carcinoma

2019 ◽  
Author(s):  
Yang Yang ◽  
Qi Mei
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Xenograft Model ◽  
Proliferation And Metastasis ◽  
Interfering Rna ◽  
Cell Proliferation And Metastasis

Abstract Background：Argonaute 2 (AGO2), a typical member of the Ago gene family, plays a pivotal role in hepatocellular carcinoma (HCC) tumorgenesis through regulating the short interfering RNA-mediated gene silencing. However, the underlined mechanism needs clarified. Herein, we found that AGO2 was frequently upregulated in human HCC cancerous tissues compared with non-cancerous tissues. Methods: Clinical analyses were performed to determine the relation between the expression level of AGO2 and prognosis in HCC patients. By using CRISPR/Cas9 approach in SMMC-7721 cells and establishing xenograft model in nude mice, we further identified the role of AGO2 in HCC. Gene expression microarray analysis was used to reveal the changes of gene expression profile mediated by AGO2 depletion in SMMC-7721 cells. Results: We observed that the overexpression of AGO2 was associated with poor prognosis in HCC patients. The knockout of AGO2 inhibited tumor cell proliferation and metastasis in vivo and in vitro. We also identified that AGO2 facilitates HCC tumorigenesis through modulating Survivin, Vimentin and Snail expression. Conclusions: Therefore, this study not only demonstrates that accumulation of AGO2 promotes cell proliferation and metastasis in HCC, but also provides a novel molecular mechanism in HCC progression.

scholarly journals The role of Neuropilin-1 in COVID-19

2021 ◽  
Vol 17 (1) ◽  
pp. e1009153
Author(s):  
Bindu S. Mayi ◽  
Jillian A. Leibowitz ◽  
Arden T. Woods ◽  
Katherine A. Ammon ◽  
Alphonse E. Liu ◽  
...  
Keyword(s):  
Immune Function ◽  
Viral Entry ◽  
Axonal Guidance ◽  
Cell Surface Receptor ◽  
Neuropilin 1 ◽  
Surface Receptor ◽  
The Central Nervous System

Neuropilin-1 (NRP-1), a member of a family of signaling proteins, was shown to serve as an entry factor and potentiate SARS Coronavirus 2 (SARS-CoV-2) infectivity in vitro. This cell surface receptor with its disseminated expression is important in angiogenesis, tumor progression, viral entry, axonal guidance, and immune function. NRP-1 is implicated in several aspects of a SARS-CoV-2 infection including possible spread through the olfactory bulb and into the central nervous system and increased NRP-1 RNA expression in lungs of severe Coronavirus Disease 2019 (COVID-19). Up-regulation of NRP-1 protein in diabetic kidney cells hint at its importance in a population at risk of severe COVID-19. Involvement of NRP-1 in immune function is compelling, given the role of an exaggerated immune response in disease severity and deaths due to COVID-19. NRP-1 has been suggested to be an immune checkpoint of T cell memory. It is unknown whether involvement and up-regulation of NRP-1 in COVID-19 may translate into disease outcome and long-term consequences, including possible immune dysfunction. It is prudent to further research NRP-1 and its possibility of serving as a therapeutic target in SARS-CoV-2 infections. We anticipate that widespread expression, abundance in the respiratory and olfactory epithelium, and the functionalities of NRP-1 factor into the multiple systemic effects of COVID-19 and challenges we face in management of disease and potential long-term sequelae.

scholarly journals SorCS3 Promotes the Internalization of p75NTR to Inhibit Glioma Progression

2021 ◽  
Author(s):  
Yanqiu Zhang ◽  
Yue Li ◽  
Yuhua Fan ◽  
Baoshan Zhao ◽  
Huan Liang ◽  
...  
Keyword(s):  
Glioma Cells ◽  
Tissue Microarrays ◽  
Cell Receptor ◽  
Receptor Internalization ◽  
Cellular Signal ◽  
Proliferation And Metastasis ◽  
The Impact ◽  
Glioma Progression

Abstract Background: Glioma is a fatal malignancy caused by dysregulation of cellular signal transduction. Internalization plays a key role in maintaining signalling balance. SorCS3 is involved in nerve cell receptor internalization. However, the impact of SorCS3 on the biological processes involved in glioma has not yet been reported. Here, we highlight the potential of SorCS3-mediated regulation of signalling receptor internalization as a rational target for therapeutic intervention in glioma.Methods: SorCS3 expression was analysed in the TCGA and CGGA databases and in tissue microarrays. The effects of SorCS3 on the proliferation and metastasis of glioma cells were examined in vitro and in vivo with Transwell, wound healing, EdU incorporation and nude mouse tumorigenicity assays. Fluorescent 5-FAM, SE-labelled proteins were used to detect the internalization of SorCS3 in glioma cells. Immunofluorescence and Co-IP assays were conducted to investigate the downstream effector of SorCS3. Moreover, Dynasore and Ro 08-2750, inhibitors of internalization and NGF binding to p75NTR, respectively, were used to validate the biological functions of SorCS3 in glioma.Results: Our data demonstrated that SorCS3 was downregulated in glioma tissues and closely related to favourable prognosis. Overexpression of SorCS3 inhibited the proliferation and metastasis of glioma cells in vitro and in vivo, while silencing of SorCS3 exerted the opposite effects. Mechanistic investigations showed that SorCS3 bound to p75NTR, which subsequently increased the internalization of p75NTR, and then transported p75NTR to the lysosome for degradation, ultimately contributing to inhibition of glioma progression.Conclusions: Our work suggests that SorSC3 is a marker of promising prognosis in glioma patients and suggests that SorCS3 regulates internalization, which plays an important role in inhibiting glioma progression.

Advances in microglia cellular models: focus on extracellular vesicle production

2021 ◽  
Author(s):  
Lorenzo Ceccarelli ◽  
Laura Marchetti ◽  
Chiara Giacomelli ◽  
Claudia Martini
Keyword(s):  
Cell Communication ◽  
Extracellular Vesicle ◽  
Cellular Models ◽  
Advantages And Disadvantages ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
Harmful Effects ◽  
Brain Homeostasis

Microglia are the major component of the innate immune system in the central nervous system. They promote the maintenance of brain homeostasis as well as support inflammatory processes that are often related to pathological conditions such as neurodegenerative diseases. Depending on the stimulus received, microglia cells dynamically change their phenotype releasing specific soluble factors and largely modify the cargo of their secreted extracellular vesicles (EVs). Despite the mechanisms at the basis of microglia actions have not been completely clarified, the recognized functions exerted by their EVs in patho-physiological conditions represent the proof of the crucial role of these organelles in tuning cell-to-cell communication, promoting either protective or harmful effects. Consistently, in vitro cell models to better elucidate microglia EV production and mechanisms of their release have been increased in the last years. In this review, the main microglial cellular models that have been developed and validated will be described and discussed, with particular focus on those used to produce and derive EVs. The advantages and disadvantages of their use will be evidenced too. Finally, given the wide interest in applying EVs in diagnosis and therapy too, the heterogeneity of available models for producing microglia EVs is here underlined, to prompt a cross-check or comparison among them.

scholarly journals Extracellular Vesicles in Human Preterm Colostrum Inhibit Infection by Human Cytomegalovirus In Vitro

2020 ◽  
Vol 8 (7) ◽  
pp. 1087
Author(s):  
Manuela Donalisio ◽  
Simona Cirrincione ◽  
Massimo Rittà ◽  
Cristina Lamberti ◽  
Andrea Civra ◽  
...  
Keyword(s):  
Breast Milk ◽  
Extracellular Vesicles ◽  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
Protective Role ◽  
Surface Proteins ◽  
Human Colostrum ◽  
Clinical Illness

Breast milk is a complex biofluid that nourishes infants, supports their growth and protects them from diseases. However, at the same time, breastfeeding is a transmission route for human cytomegalovirus (HCMV), with preterm infants being at a great risk of congenital disease. The discrepancy between high HCMV transmission rates and the few reported cases of infants with severe clinical illness is likely due to the protective effect of breast milk. The aim of this study was to investigate the anti-HCMV activity of human preterm colostrum and clarify the role of colostrum-derived extracellular vesicles (EVs). Preterm colostrum samples were collected and the EVs were purified and characterized. The in vitro anti-HCMV activity of both colostrum and EVs was tested against HCMV, and the viral replication step inhibited by colostrum-purified EVs was examined. We investigated the putative role EV surface proteins play in impairing HCMV infection using shaving experiments and proteomic analysis. The obtained results confirmed the antiviral action of colostrum against HCMV and demonstrated a remarkable antiviral activity of colostrum-derived EVs. Furthermore, we demonstrated that EVs impair the attachment of HCMV to cells, with EV surface proteins playing a role in mediating this action. These findings contribute to clarifying the mechanisms that underlie the protective role of human colostrum against HCMV infection.

scholarly journals Intranasal Borna Disease Virus (BoDV-1) Infection: Insights into Initial Steps and Potential Contagiosity

2019 ◽  
Vol 20 (6) ◽  
pp. 1318 ◽  
Author(s):  
Alexandra Kupke ◽  
Sabrina Becker ◽  
Konstantin Wewetzer ◽  
Barbara Ahlemeyer ◽  
Markus Eickmann ◽  
...  
Keyword(s):  
Viral Infections ◽  
Cell Types ◽  
Nerve Fibers ◽  
Olfactory Pathway ◽  
Adult Rats ◽  
The Central Nervous System ◽  
Receptor Neurons

Mammalian Bornavirus (BoDV-1) typically causes a fatal neurologic disorder in horses and sheep, and was recently shown to cause fatal encephalitis in humans with and without transplant reception. It has been suggested that BoDV-1 enters the central nervous system (CNS) via the olfactory pathway. However, (I) susceptible cell types that replicate the virus for successful spread, and (II) the role of olfactory ensheathing cells (OECs), remained unclear. To address this, we studied the intranasal infection of adult rats with BoDV-1 in vivo and in vitro, using olfactory mucosal (OM) cell cultures and the cultures of purified OECs. Strikingly, in vitro and in vivo, viral antigen and mRNA were present from four days post infection (dpi) onwards in the olfactory receptor neurons (ORNs), but also in all other cell types of the OM, and constantly in the OECs. In contrast, in vivo, BoDV-1 genomic RNA was only detectable in adult and juvenile ORNs, nerve fibers, and in OECs from 7 dpi on. In vitro, the rate of infection of OECs was significantly higher than that of the OM cells, pointing to a crucial role of OECs for infection via the olfactory pathway. Thus, this study provides important insights into the transmission of neurotropic viral infections with a zoonotic potential.

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