miR-663 Suppresses Oncogenic Function of <i>CXCR4</i> in Glioblastoma

Shi, Yu; Chen, Cong; Yu, Shizhu; Liu, Qing; Rao, Jun; Zhang, Huarong; Xiao, Hualiang; Fu, Tiwei; Long, Hua; He, Zhicheng; Zhou, Kai; Yao, Xiaohong; Cui, You‐Hong; Zhang, Xia; Ping, Yi‐Fang; Bian, Xiu‐Wu

doi:10.1158/1078-0432.ccr-14-2807

Cited by 55 publications

(44 citation statements)

References 37 publications

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“…The present study shows that CXCR4 expression was reduced in over-expressing miR-663a HCT116 cells, which resulted in the suppression of proliferation. Yu et al reports that miR-663a negatively regulates CXCR4 expression by targeting its coding sequence in human glioblastoma cells and compromises proliferation [34]. This report suggests that miR-663a directly binds to the coding sequence of CXCR4 mRNA to suppress its translation.…”

Section: Discussionmentioning

confidence: 99%

miR-663a regulates growth of colon cancer cells, after administration of antimicrobial peptides, by targeting CXCR4-p21 pathway

et al. 2017

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BackgroundAntimicrobial peptides (AMPs) play important roles in the innate immune system of all life forms and recently have been characterized as multifunctional peptides that have a variety of biological roles such as anticancer agents. However, detailed mechanism of antimicrobial peptides on cancer cells is still largely unknown.MethodsmiRNA array and real-time qPCR were performed to reveal the behavior of miRNA in colon cancer HCT116 cells during the growth suppression induced by the AMPs. Establishment of miR-663a over-expressing HCT116 cells was carried out for the evaluation of growth both in vitro and in vivo. To identify the molecular mechanisms, we used western blotting analysis.ResultsmiR-663a is upregulated by administration of the human cathelicidin AMP, LL-37, and its analogue peptide, FF/CAP18, in the colon cancer cell line HCT116. Over-expression of miR-663a caused anti-proliferative effects both in vitro and in vivo. We also provide evidence supporting the view that these effects are attributed to suppression of the expression of the chemokine receptor CXCR4, resulting in the abrogation of phosphorylation of Akt and cell cycle arrest in G2/M via p21 activation.ConclusionsThis study contributes to the understanding of the AMPs’ mediated anti-cancer mechanisms in colon cancer cells and highlights the possibility of using AMPs and miRNAs towards developing future strategies for cancer therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-3003-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

miR-663a regulates growth of colon cancer cells, after administration of antimicrobial peptides, by targeting CXCR4-p21 pathway

et al. 2017

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“…Immunoblot analyses were performed as previously described. 8,44 The primary antibodies used in this study include the following: anti-CD9 (sc- Ubiquitination assay. Ubiquitination assay was performed as previously described.…”

Section: Methodsmentioning

confidence: 99%

“…qRT-PCR was performed using a Bio-Rad CFX96 Real-Time PCR Detection System (Bio-rad, Hercules, CA, USA) or an ABI 7900HT Sequence Detection System (Applied Biosystems, Foster City, CA, USA) as previously described. 8,44 The primer sequences were listed in Supplementary Table S6. Expression of GAPDH was used for the normalization.…”

Section: Methodsmentioning

confidence: 99%

Tetraspanin CD9 stabilizes gp130 by preventing its ubiquitin-dependent lysosomal degradation to promote STAT3 activation in glioma stem cells

et al. 2016

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Glioblastoma (GBM) is the most malignant and lethal brain tumor harboring glioma stem cells (GSCs) that promote tumor propagation and therapeutic resistance. GSCs preferentially express several critical cell surface molecules that regulate the prosurvival signaling for maintaining the stem cell-like phenotype. Tetraspanin CD9 has recently been reported as a GSC biomarker that is relevant to the GSC maintenance. However, the underlying molecular mechanisms of CD9 in maintaining GSC property remain elusive. Herein, we report that CD9 stabilizes the IL-6 receptor glycoprotein 130 (gp130) by preventing its ubiquitindependent lysosomal degradation to facilitate the STAT3 activation in GSCs. CD9 is preferentially expressed in GSCs of human GBM tumors. Mass spectrometry analysis identified gp130 as an interacting protein of CD9 in GSCs, which was confirmed by immunoprecipitation and immunofluorescent analyses. Disrupting CD9 or gp130 by shRNA significantly inhibited the self-renewal and promoted the differentiation of GSCs. Moreover, CD9 disruption markedly reduced gp130 protein levels and STAT3 activating phosphorylation in GSCs. CD9 stabilized gp130 by preventing its ubiquitin-dependent lysosomal degradation to promote the BMX-STAT3 signaling in GSCs. Importantly, targeting CD9 potently inhibited GSC tumor growth in vivo, while ectopic expression of the constitutively activated STAT3 (STAT3-C) restored the tumor growth impaired by CD9 disruption. Collectively, we uncovered a critical regulatory mechanism mediated by tetraspanin CD9 to maintain the stem cell-like property and tumorigenic potential of GSCs.

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“…CXCR4 and NR5A2 are all reported to be associated with the progression of human cancers [49][50][51][52]. Besides, CXCR4 has been proved to be related to GBM [53,54]. As to NR5A2, it encodes a DNA-binding zinc finger transcription factor protein and involved in the expression of genes for hepatitis B virus and cholesterol biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

Systemic analysis of lncRNA and miRNA expression profiles with associated ceRNA network in glioblastoma

Sun¹,

Liu²,

Song³

et al. 2018

Oncotarget

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Glioblastoma (GBM) is the most common malignant brain tumor with high morbidity and mortality. Long and small non-coding RNA, i.e. lncRNA and miRNA in this study, play important roles in progression of complex diseases and competes with each other when regulate expression of mRNA. In this study, we conducted systemic analysis of high-throughput gene sequencing and microarray datasets to explore expression regulation patterns in GBM. Differential expression mRNAs, lncRNAs and miRNAs were obtained through comprehensively comparinged their expression profiles between GBM and adjacent non-tumor tissues. As a result, a total of 28 lncRNAs were found to be aberrantly expressed (|log2 (fold change)| > 1, corrected p-value < 0.01) and six out of them were significantly associated with GBM prognosis. The expression changes of the six lncRNAs were further validated through quantative PCR analysis. Finally, lncRNA mediated competition endogenous (ceRNA) network was constructed, which should be helpful for the understanding of lncRNA mediated ceRNA network and identification of prognosis biomarker for GBM.

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miR-663 Suppresses Oncogenic Function of CXCR4 in Glioblastoma

Cited by 55 publications

References 37 publications

miR-663a regulates growth of colon cancer cells, after administration of antimicrobial peptides, by targeting CXCR4-p21 pathway

miR-663a regulates growth of colon cancer cells, after administration of antimicrobial peptides, by targeting CXCR4-p21 pathway

Tetraspanin CD9 stabilizes gp130 by preventing its ubiquitin-dependent lysosomal degradation to promote STAT3 activation in glioma stem cells

Systemic analysis of lncRNA and miRNA expression profiles with associated ceRNA network in glioblastoma

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