CBMS-12 Pro renin receptor antibody regulates glioblastoma stemness

Abstract Objective: Glioblastoma multiforme (GBM) is characterized by a strong self-renewal potential and poor differentiated state. We previously reported that (pro)renin receptor (PRR) was a potential target for glioma therapy by silencing the gene of PRR. Here, we have developed the monoclonal antibody of PRR and examined their effects on GBM. Materials and methods: We performed immunohistochemical analysis to detect the protein expression of PRR and SOX-2 in human sample of 56 gliomas. We used human glioma cell lines (U251MG and U87MG) and glioma stem cell line (MGG23) in vitro study. PRR antibody was designed to target the extracellular domain of the PRR with the rat lymph node method. Expression of the Wnt signaling components and stem marker (SOX-2, Oct3/4) in human glioma cell lines and glioma stem cell line treated with PRR antibody were measured using Western blotting. The effects of PRR antibody on cell proliferation, sphere formation, apoptosis, invasion were also examined. Subcutaneous xenografts with U87MG were induced in nude mice. Results: PRR expression showed a positive correlation with SOX-2 expression in glioma samples. Treatment with PRR antibody significantly reduced expression of Wnt signaling components and stem marker. We observed that PRR antibody significantly reduced cell proliferation and decreased sphere formation. Furthermore, PRR antibody suppressed invasion and induced apoptosis. In a subcutaneous U87MG xenograft model, systemic administration of the PRR antibody significantly reduced the size of the tumor volume. Conclusion: PRR has important role for the maintenance of stem cells and contribute to stem cell proliferation. PRR antibody inhibits cell proliferation and cell invasion and induces apoptosis. Treatment with PRR antibody could be an attractive therapeutic strategy for GBM.

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Long Intergenic Noncoding RNA 00152 Promotes Glioma Cell Proliferation and Invasion by Interacting with MiR-16

Cellular Physiology and Biochemistry ◽

10.1159/000488836 ◽

2018 ◽

Vol 46 (3) ◽

pp. 1055-1064 ◽

Cited By ~ 12

Author(s):

Xin Chen ◽

Deheng Li ◽

Yang Gao ◽

Wei Tang ◽

Lao IW ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Glioma Cell ◽

Migration And Invasion ◽

Human Glioma ◽

Human Glioma Cell ◽

Glioma Cell Lines ◽

Glioma Cell Proliferation ◽

Proliferation And Invasion

Background/Aims: Long noncoding RNAs (lncRNAs) are a novel class of protein-noncoding transcripts that are aberrantly expressed in multiple diseases including cancers. LINC00152 has been identified as an oncogene involved in many kinds of cancer; however, its expression pattern and function in human glioma remain unclear. Methods: Quantitative real-time polymerase chain reaction was carried out to measure LINC00152 expression in human glioma cell lines and tissues. CCK-8 and EdU assays were performed to assess cell proliferation, and scratch assays and Transwell assays were used to assess cell migration and invasion, respectively. Luciferase reporter assays were carried out to determine the interaction between miR-16 and LINC00152. In vivo experiments were conducted to assess tumor formation. Results: LINC00152 was found to be significantly upregulated in human glioma cell lines and clinical samples. Knockdown of LINC00152 suppressed glioma cell proliferation, migration, and invasion in vitro. In vivo assays in nude mice confirmed that LINC00152 knockdown inhibits tumor growth. Furthermore, mechanistic investigation showed that LINC00152 binds to miR-16 in a sequence-specific manner and suppresses its expression. miR-16 inhibition strongly attenuated LINC00152 knockdown–mediated suppressive effects on proliferation, migration, and invasion. Moreover, LINC00152 induced BMI1 expression by sponging miR-16; this effect further promoted glioma cell proliferation and invasion. Conclusion: We regard LINC00152 as an oncogenic lncRNA promoting glioma cell proliferation and invasion and as a potential target for human glioma treatment.

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5-lipoxygenase pathway promotes cell proliferation in human glioma cell lines

Clinical Neuropathology ◽

10.5414/npp28445 ◽

2009 ◽

Vol 28 (11) ◽

pp. 445-452 ◽

Cited By ~ 22

Author(s):

K. Ishii ◽

M. Zaitsu ◽

N. Yonemitsu ◽

Y. Kan ◽

Y. Hamasaki ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Glioma Cell ◽

Human Glioma ◽

Lipoxygenase Pathway ◽

Human Glioma Cell ◽

Glioma Cell Lines

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Preferential Expression of B7-H6 in Glioma Stem-Like Cells Enhances Tumor Cell Proliferation via the c-Myc/RNMT Axis

Journal of Immunology Research ◽

10.1155/2020/2328675 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Hanqing Chen ◽

Yundi Guo ◽

Jing Sun ◽

Jun Dong ◽

Qinghua Bao ◽

...

Keyword(s):

Cell Proliferation ◽

Stem Cell ◽

Cell Lines ◽

Glioma Cell ◽

Nk Cell ◽

Costimulatory Molecule ◽

Mapk Signaling ◽

Stem Cell Marker ◽

Glioma Tissue ◽

Glioma Cell Lines

B7 homologue 6 (B7-H6), a newly identified member of the B7 costimulatory molecule family, is not only a crucial regulator of NK cell-mediated immune responses through binding to NKp30 but also has clinical implications due to its abnormal expression in human cancers. Here, we show that B7-H6 expression is abnormally upregulated in glioma tissue and that B7-H6 is coexpressed with stem cell marker Sox2. Intriguingly, B7-H6 was rarely detected on the surface of glioma cell lines but was abundantly expressed in glioma stem-like cells (GSLCs) that were derived from the glioma cell lines in vitro. Surprisingly, B7-H6 was the only one that was preferentially expressed in the GSLCs among the B7 family members. Functionally, knockdown of B7-H6 in GSLCs by siRNAs led to the inhibition of cell proliferation, with decrease in the expression of the oncogene Myc as well as inactivation of PI3K/Akt and ERK/MAPK signaling pathways. Moreover, we determined that three genes CBL (Casitas B-Lineage Lymphoma Proto-Oncogene), CCNT1 (Cyclin T1), and RNMT (RNA guanine-7 methyltransferase) were coexpressed with B7-H6 and c-myc in glioma tissue samples from the TCGA database and found, however that only RNMT expression was inhibited by the knockdown of B7-H6 expression in the GSLCs, suggesting the involvement of RNMT in the B7-H6/c-myc axis. Extending this to 293T cells, we observed that knocking out of B7-H6 with CRISPR-Cas9 system also suppressed cell proliferation. Thus, our findings suggest B7-H6 as a potential molecule for glioma stem cell targeted immunotherapy.

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Cyclic GMP-dependent protein kinase II inhibits cell proliferation, Sox9 expression and Akt phosphorylation in human glioma cell lines

Oncogene ◽

10.1038/onc.2009.168 ◽

2009 ◽

Vol 28 (35) ◽

pp. 3121-3131 ◽

Cited By ~ 57

Author(s):

F J Swartling ◽

M Ferletta ◽

M Kastemar ◽

W A Weiss ◽

B Westermark

Keyword(s):

Cell Proliferation ◽

Protein Kinase ◽

Cyclic Gmp ◽

Glioma Cell ◽

Human Glioma ◽

Dependent Protein Kinase ◽

Sox9 Expression ◽

Akt Phosphorylation ◽

Glioma Cell Lines ◽

Dependent Protein

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Human wild type p53 inhibits cell proliferation and elicits dramatic morphological changes in human glioma cell lines in vitro

Journal of the Neurological Sciences ◽

10.1016/0022-510x(94)90064-7 ◽

1994 ◽

Vol 127 (2) ◽

pp. 125-133 ◽

Cited By ~ 17

Author(s):

Abderrahim Merzak ◽

Stéphane Raynal ◽

Joan P. Rogers ◽

David Lawrence ◽

Geoffrey J. Pilkington

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Glioma Cell ◽

Morphological Changes ◽

Human Glioma ◽

Wild Type ◽

Human Glioma Cell ◽

Glioma Cell Lines ◽

Human Wild Type

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Long Noncoding RNA H19 Promotes Proliferation and Invasion in Human Glioma Cells by Downregulating miR-152

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504018x15178768577951 ◽

2018 ◽

Vol 26 (9) ◽

pp. 1419-1428 ◽

Cited By ~ 18

Author(s):

Lei Chen ◽

Yuhai Wang ◽

Jianqing He ◽

Chunlei Zhang ◽

Junhui Chen ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Glioma Cell ◽

Glioma Cells ◽

Human Glioma ◽

Human Glioma Cell ◽

Glioma Cell Lines ◽

Glioma Cell Proliferation ◽

Proliferation And Invasion

miR-152 and lncRNA H19 have been frequently implicated in various cellular processes including cell proliferation, invasion, angiogenesis, and apoptosis. However, the interaction between miR-152 and H19 in glioma has never been reported. RT-qPCR was used to examine the expression of miR-152 and H19 in human glioma cell lines and normal human astrocytes (NHAs). The interaction between miR-152 and lncRNA H19 was assessed by dual-luciferase reporter assay. MTT assay and Transwell invasion assay were used to determine the proliferation and invasion of U251 and U87 cells. A xenograft tumor experiment was performed to confirm the role of H19 in vivo. The results showed that H19 expression was upregulated and miR-152 expression was downregulated in human glioma cell lines. H19 downregulation or miR-152 upregulation suppressed glioma cell proliferation and invasion in vitro. Moreover, H19 and miR-152 directly regulated each other. Furthermore, decreased miR-152 expression alleviated si-H19-induced inhibitory effects on proliferation and invasion in glioma cells. As expected, H19 silencing hindered glioma growth in vivo. Taken together, H19 promoted glioma cell proliferation and invasion by negatively regulating miR-152 expression, providing evidence for the potential application of H19 as a biomarker and therapy target for glioma.

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ET-04 MOLECULAR TARGETED THERAPY AGAINST (PRO)RENIN RECEPTOR FOR GLIOBLASTOMA

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz039.038 ◽

2019 ◽

Vol 1 (Supplement_2) ◽

pp. ii8-ii9

Author(s):

Takeshi Fujimori ◽

Daisuke Ogawa ◽

Kenta Suzuki ◽

Masaaki Kochi ◽

Yuki Shibayama ◽

...

Keyword(s):

Flow Cytometry ◽

Cell Proliferation ◽

Stem Cell ◽

Wnt Signaling ◽

Cell Line ◽

Annexin V ◽

Stem Cell Markers ◽

Glioma Stem Cell ◽

Cell Markers ◽

Induced Apoptosis

Abstract INTRODUCTION (Pro)renin receptor(PRR) is part of the Wnt receptor complex. Wnt/β-catenin signaling pathway (Wnt signaling) plays important role in pathogenesis and self-renewal of glioblastoma (GBM), or differentiation of glioma stem cell. We previously reported that PRR activate Wnt signaling, PRR expression correlated with malignancy of glioma, and treatment with PRR siRNA reduced the proliferative capacity. This time, we have developed monoclonal antibodies against PRR and examined their effects in GBM. MATERIAL AND METHODS We used GBM cell line (U251MG and U87MG) and primary human glioma stem cell line (MGG23). Glioma stem-like cells were cultured and isolated by neurosphere method from U251MG and U87MG. PRR antibody was made targeting the extracellular domain of the PRR with rat lymph node method. WST-1 assay or MTT assay were performed to determine the cell proliferation. Apoptosis was examined by FITC labeled annexin V and propidium iodide with flow cytometry. We analyzed molecules of Wnt signaling and stem cell markers with qRT-PCR. RESULTS We observed that PRR antibody significantly reduced cell proliferation, decreased sphere formation. Antibody suppressed cell adherent in stem-like cell. Flow cytometry showed that antibody induced apoptosis. Antibody inhibited Wnt signaling and stem cell markers. CONCLUSIONS PRR antibody reduced cell proliferation and induced apoptosis through Wnt signaling. PRR antibody also suppressed stemness. Our results demonstrated that PRR was a potential target for future glioma therapy.

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