scholarly journals Silencing myelin protein zero-like 1 expression suppresses cell proliferation and invasiveness of human glioma cells by inhibiting multiple cancer-associated signal pathways

2021 ◽  
Vol 9 (4) ◽  
pp. 229-244
Author(s):  
Simiao Zhang ◽  
Sandian Zhang ◽  
Hongzhen Wang ◽  
Xuege Huang ◽  
Jinzhi Wang ◽  
...  

Glioma is the most common primary malignant tumor of the adult central nervous system. It has high morbidity and poor survival. Myelin protein zero-like protein 1 (MPZL1) is a cell surface glycoprotein that activates numerous adhesion-dependent signaling pathways. MPZL1 plays important roles in human cancers that include metastatic process; however, it is not clear if MPZL1 plays a role in human glioma. Therefore, this study aimed to determine if silencing MPZL1 impacted the cell proliferative features of human glioma cells. First, MPZL1 expression was investigated in human glioma samples and tumor cell lines. Then the effects of small interfering RNA (siRNA)-targeting MPZL1 were analyzed on proliferation, colony formation, cell cycle progression, and invasion of human glioma cells. The results from this study demonstrated that MPZL1 was highly expressed in human glioma tissues and glioma cell lines. In addition, knockdown of MPZL1 significantly inhibited cell proliferation, colony formation, and invasiveness of glioma cells, and effectively induced cell cycle arrest at the G1 phase. Western blotting analysis indicated that silencing MPZL1 expression downregulated the expression of matrix metalloproteinase-2 (MMP-2), WNT1, caspase-3, cyclin A1, epidermal growth factor receptor (EGFR), and signal transducer and activator of transcription 3 (STAT3), and upregulated p53. The results from this study suggest that MPZL1 might be a marker for tumors and could be a potential therapeutic target for human glioma.

2020 ◽  
Vol 52 (12) ◽  
pp. 1394-1403
Author(s):  
Tuo Wang ◽  
Yan Zhang ◽  
Bo Cui ◽  
Maode Wang ◽  
Ya Li ◽  
...  

Abstract Human glioma is the most common primary brain tumor and is associated with high morbidity and mortality. Aberrant expressions of microRNAs (miRNAs) are involved in glioma progression. In the present study, we aimed to elucidate the roles of miR-4530 in the pathogenesis of gliomas. miR-4530 expression was examined in human glioma clinical tissues and cell lines including U251 and T98G. The target gene of miR-4530, RTEL1, was predicted with online tools and validated by luciferase reporter assay. Lentivirus infection, transfection of plasmids, and miRNA mimics were used to manipulate gene expression. Cell proliferation was determined using the CCK-8 method, and migration and invasion assays were determined with transwell experiments. Colony formation was measured by crystal violet staining, while apoptosis was determined by Annexin V/PI staining. The anti-tumor effects of miR-4530 were evaluated in nude mice xenografted using U251 cells. Our results showed that miR-4530 was significantly down-regulated in human glioma tissues and cell lines. miR-4530 over-expression inhibited the malignant behaviors of U251 and T98G cells, including reduced proliferation, diminished colony formation, migration and invasion, and increased apoptosis. Further mechanistic investigations revealed that RTEL1 is a direct functional target of miR-4530 in gliomas, and its over-expression remarkably reverses the effects of miR-4530 mimics on inhibiting these malignant behaviors. In addition, miR-4530 over-expression inhibited the growth of xenografted U251 glioma in nude mice. Therefore, miR-4530 acts as a tumor-suppressor gene and inhibits the malignant biological behaviors of human glioma cells, which is associated with directly targeting RTEL1. The miR-4530/RTEL1 axis is a potential therapeutic target for gliomas.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Wangsheng Chen ◽  
Lan Hong ◽  
Changlong Hou ◽  
Yibin Wang ◽  
Fei Wang ◽  
...  

Abstract Background MicroRNAs (miRNAs) are important regulators for cancer cell proliferation. miR-585 has been shown to inhibit the proliferation of several types of cancer, however, little is known about its role in human glioma cells. Methods miR-585 levels in human glioma clinical samples and cell lines were examined by quantitative real-time PCR (qRT-PCR) analysis. Cell proliferation was measured by Cell Counting Kit-8 (CCK-8) and EdU incorporation assays in vitro. For in vivo investigations, U251 cells were intracranially inoculated in BALB/c nude mice and xenografted tumors were visualized by magnetic resonance imaging (MRI). Results miR-585 expression is downregulated in human glioma tissues and cell lines compared with non-cancerous counterparts. Additionally, miR-585 overexpression inhibits and its knockdown promotes human glioma cell proliferation in vitro. Moreover, miR-585 overexpression also inhibits the growth of glioma xenografts in vivo, suggesting that miR-585 may act as a tumor suppressor to inhibit the proliferation of human glioma. Furthermore, miR-585 directly targets and decreases the expression of oncoprotein murine double minute 2 (MDM2). More importantly, the restoration of MDM2 via enforced overexpression markedly rescues miR-585 inhibitory effect on human glioma cell proliferation, thus demonstrating that targeting MDM2 is a critical mechanism by which miR-585 inhibits human glioma cell proliferation. Conclusions Our study unveils the anti-proliferative role of miR-585 in human glioma cells, and also implicates its potential application in clinical therapy.


2016 ◽  
Vol 13 (2) ◽  
pp. 1007-1013 ◽  
Author(s):  
Aisha Maimaitili ◽  
Zunhua Shu ◽  
Xiaojiang Cheng ◽  
Kadeer Kaheerman ◽  
Alifu Sikandeer ◽  
...  

1995 ◽  
Vol 82 (6) ◽  
pp. 1035-1043 ◽  
Author(s):  
Jörg-Christian Tonn ◽  
Hans Kristian Haugland ◽  
Jaakko Saraste ◽  
Klaus Roosen ◽  
Ole Didrik Laerum

✓ The aim of this study was to investigate the antimigratory and antiinvasive potential of vincristine sulfate (VCR) on human glioma cells and to analyze whether phenytoin (5,5-diphenylhydantoin; DPH) might act synergistically with VCR. Vincristine affects the cytoplasmic microtubules; DPH has been reported to enhance VCR cytotoxicity in murine cells. In two human glioma cell lines, GaMG and D-37MG, we found VCR to reduce monolayer growth and colony formation in a dose-dependent fashion at concentrations of 10 ng/ml and above. Phenytoin increased the cytotoxic and cystostatic effects of VCR in monolayer cells but not in spheroids. Multicellular spheroids were used to investigate directional migration. A coculture system of GaMG and D-37MG spheroids with fetal rat brain aggregates was used to analyze and quantify tumor cell invasion. A dose-dependent inhibition of migration and invasion by VCR was observed in both cell lines without further enhancement by DPH. Immunofluorescence microscopy with antibodies against α-tubulin revealed dose-dependent morphological alterations in the microtubules when the cells were exposed to VCR but not after incubation with DPH. Based on the combination of standardized in vitro model systems currently in use and the present data, the authors strongly suggest that VCR inhibits migration and invasion of human glioma cells. This is not altered by DPH, which inhibits cell proliferation in combination with VCR.


2003 ◽  
Vol 84 (6) ◽  
pp. 1288-1295 ◽  
Author(s):  
Mara D'Onofrio ◽  
Antonietta Arcella ◽  
Valeria Bruno ◽  
Richard T. Ngomba ◽  
Giuseppe Battaglia ◽  
...  

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