Primate-Specific miR-663 Functions as a Tumor Suppressor by Targeting <i>PIK3CD</i> and Predicts the Prognosis of Human Glioblastoma

Shi, Yu; Chen, Cong; Zhang, Xia; Liu, Qing; Xu, Jinling; Zhang, Huarong; Yao, Xiaohong; Jiang, Tao; He, Zhicheng; Ren, Yong; Cui, Wei; Xu, Chuan; Liu, Ling; Cui, You‐Hong; Yu, Shizhu; Ping, Yi‐Fang; Bian, Xiu‐Wu

doi:10.1158/1078-0432.ccr-13-2284

Cited by 82 publications

(74 citation statements)

References 45 publications

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“…All specimens were collected during surgery with written informed consents from the patients, and their use for immunohistochemical staining was approved by the Ethics Committee of Southwest Hospital, Third Military Medical University, China. Immunohistochemistry analysis of WHO grade I to IV gliomas and semiquantitative analysis of CD146 expression were performed as previously described using YY146 as the primary antibody (36). Briefly, tumor specimens were surgically removed from patients, and their WHO classification was determined by two or more neuropathologists.…”

Section: Rna Isolation and Rt-pcrmentioning

confidence: 99%

Targeting CD146 with a ⁶⁴ Cu-labeled antibody enables in vivo immunoPET imaging of high-grade gliomas

Yang

Hernandez

Rao

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Given the highly heterogeneous character of brain malignancies and the associated implication for its proper diagnosis and treatment, finding biomarkers that better characterize this disease from a molecular standpoint is imperative. In this study, we evaluated CD146 as a potential molecular target for diagnosis and targeted therapy of glioblastoma multiforme (GBM), the most common and lethal brain malignancy. YY146, an anti-CD146 monoclonal antibody, was generated and radiolabeled for noninvasive positron-emission tomography (PET) imaging of orthotopic GBM models. 64Cu-labeled YY146 preferentially accumulated in the tumors of mice bearing U87MG xenografts, which allowed the acquisition of high-contrast PET images of small tumor nodules (∼2 mm). Additionally, we found that tumor uptake correlated with the levels of CD146 expression in a highly specific manner. We also explored the potential therapeutic effects of YY146 on the cancer stem cell (CSC) and epithelial-to-mesenchymal (EMT) properties of U87MG cells, demonstrating that YY146 can mitigate those aggressive phenotypes. Using YY146 as the primary antibody, we performed histological studies of World Health Organization (WHO) grades I through IV primary gliomas. The positive correlation found between CD146-positive staining and high tumor grade (χ2 = 9.028; P = 0.029) concurred with the GBM data available in The Cancer Genome Atlas (TCGA) and validated the clinical value of YY146. In addition, we demonstrate that YY146 can be used to detect CD146 in various cancer cell lines and human resected tumor tissues of multiple other tumor types (gastric, ovarian, liver, and lung), indicating a broad applicability of YY146 in solid tumors.

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Section: Rna Isolation and Rt-pcrmentioning

confidence: 99%

Targeting CD146 with a ⁶⁴ Cu-labeled antibody enables in vivo immunoPET imaging of high-grade gliomas

Yang

Hernandez

Rao

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Tumor cell proliferation and invasion assays were performed as previously described (10). Cell Counting Kit-8 (Beyotime) was used to examine the proliferative capacity of GBM cells.…”

Section: Tumor Cell Proliferation and Invasion Assaysmentioning

confidence: 99%

“…Real-time qRT-PCR was performed as previously described (10). Specific primer sets for miR-663 and U6 were purchased from RiboBio.…”

Section: Real-time Qrt-pcrmentioning

confidence: 99%

“…The human miR-663-overexpressing CMV-mCherry lentiviral vector was generated as previously described (10). To construct the doxycycline-induced miR-663-expressing vector, the mCherry-pre-miR-663 sequence from human miR-663 overexpressing vector was cloned into the pCW-Cas9 vector (Addgene) with the primers listed in Supplementary Table S2.…”

Section: Lentiviral Vectors Productionmentioning

confidence: 99%

“…MicroRNAs (miRNAs), which modulate gene expression at the posttranscriptional level, provide potential mechanisms of epigenetic regulation in cancer development (9)(10)(11). Recent studies emphasized that manipulation of miRNAs and their oligonucleotide antagonists, including miRNA-based nanodrugs, miRNA mimics, miRNA sponge and miR-mask, represents an attractive approach for antitumor therapy (12,13).…”

Section: Introductionmentioning

confidence: 99%

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miR-663 Suppresses Oncogenic Function of CXCR4 in Glioblastoma

Shi

Chen

et al. 2015

Clinical Cancer Research

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Purpose: To identify the miRNA regulators of C-X-C motif chemokine receptor 4 (CXCR4) and the underlying mechanism as well as the therapeutic and prognostic values in human glioblastoma (GBM).Experimental Design: miRNA profile analyses and bioinformatics predictions were used to identify the mediators of CXCR4, which were confirmed by luciferase reporter assay, Western blot assay and immunohistochemistry. The effects of miR-663 on CXCR4-mediated GBM malignancy were investigated by gainof-function experiments. Orthotopic xenografts derived from constitutive or induced miR-663-expressing GBM cells were used to determine the antitumor effects of miR-663 and CXCR4-specific antagonist AMD3100. Bivariate correlation analyses were used to examine the correlation of miR-663 and CXCR4 levels in glioma. The prognostic values of miR-663 and CXCR4 were examined in 281 cases of astrocytic glioma from our hospital and 476 cases of GBM from The Cancer Genome Atlas database using the multivariate Cox regression analysis and Kaplan-Meier analysis.Results: miR-663 negatively regulated CXCR4 expression by targeting its coding sequence in GBM and compromised the proliferative and invasive capacities of GBM cells induced by CXCR4 overexpression. Constitutive or induced miR-663 overexpression combined with CXCR4 antagonist AMD3100 suppressed orthotopic GBM growth and prolonged tumor-bearing mice survival. Clinically, miR-663 and CXCR4 were inversely correlated in GBM and composed a valuable biomarker set in predicting the outcomes of GBM patients.Conclusions: miR-663 negatively regulated CXCR4 to inhibit its oncogenic effect. Combination of miR-663 and CXCR4 can serve as a valuable prognostic biomarker set as well as molecular targets for therapeutic intervention of GBM.

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ASCL2 Maintains Stemness Phenotype through ATG9B and Sensitizes Gliomas to Autophagy Inhibitor

et al. 2022

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Autophagy is a highly conserved process that is vital for tumor progression and treatment response. Although autophagy is proposed to maintain the stemness phenotype in adult diffuse glioma, the molecular basis of the link between autophagy and stemness is poorly understood, which makes it impossible to effectively screen for the population that will benefit from autophagy‐targeted treatment. Here, ATG9B as essential for self‐renewal capacity and tumor‐propagation potential is identified. Notably, ASCL2 transcriptionally regulates the expression of ATG9B to maintain stemness properties. The ASCL2‐ATG9B axis is an independent prognostic biomarker and indicator of autophagic activity. Furthermore, the highly effective blood–brain barrier (BBB)‐permeable autophagy inhibitor ROC‐325, which can significantly inhibit the progression of ASCL2‐ATG9B axisHigh gliomas as a single agent is investigated. These data demonstrate that a new ASCL2‐ATG9B signaling axis is crucial for maintaining the stemness phenotype and tumor progression, revealing a potential autophagy inhibition strategy for adult diffuse gliomas.

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Primate-Specific miR-663 Functions as a Tumor Suppressor by Targeting PIK3CD and Predicts the Prognosis of Human Glioblastoma

Cited by 82 publications

References 45 publications

Targeting CD146 with a ⁶⁴ Cu-labeled antibody enables in vivo immunoPET imaging of high-grade gliomas

Targeting CD146 with a ⁶⁴ Cu-labeled antibody enables in vivo immunoPET imaging of high-grade gliomas

miR-663 Suppresses Oncogenic Function of CXCR4 in Glioblastoma

ASCL2 Maintains Stemness Phenotype through ATG9B and Sensitizes Gliomas to Autophagy Inhibitor

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Primate-Specific miR-663 Functions as a Tumor Suppressor by Targeting PIK3CD and Predicts the Prognosis of Human Glioblastoma

Cited by 82 publications

References 45 publications

Targeting CD146 with a 64 Cu-labeled antibody enables in vivo immunoPET imaging of high-grade gliomas

Targeting CD146 with a 64 Cu-labeled antibody enables in vivo immunoPET imaging of high-grade gliomas

miR-663 Suppresses Oncogenic Function of CXCR4 in Glioblastoma

ASCL2 Maintains Stemness Phenotype through ATG9B and Sensitizes Gliomas to Autophagy Inhibitor

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Targeting CD146 with a ⁶⁴ Cu-labeled antibody enables in vivo immunoPET imaging of high-grade gliomas

Targeting CD146 with a ⁶⁴ Cu-labeled antibody enables in vivo immunoPET imaging of high-grade gliomas