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Zhu-Mei Shi, Xie-Feng Wang,
Xu Qian,
Tao Tao,
Lin Wang,
Qiu-Dan Chen,
Xi-Rui Wang,
Lei Cao,
Ying-Yi Wang,
Jun-Xia Zhang,
Tao Jiang,
Chun-Sheng Kang,
Bing-Hua Jiang,
Ning Liu,
Yong-Ping You
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ABSTRACT: MicroRNAs (miRNAs) are single-stranded, 18- to 23-nt RNA molecules that function as regulators of gene expression. Previous studies have shown that microRNAs play important roles in human cancers, including gliomas. Here, we found that expression levels of miR-181b were decreased in gliomas, and we identified IGF-1R as a novel direct target of miR-181b. MiR-181b overexpression inhibited cell proliferation, migration, invasion, and tumorigenesis by targeting IGF-1R and its downstream signaling pathways, PI3K/AKT and MAPK/ERK1/2. Overexpression of IGF-1R rescued the inhibitory effects of miR-181b. In clinical specimens, IGF-1R was overexpressed, and its protein levels were inversely correlated with miR-181b expression. Taken together, our results indicate that miR-181b functions in gliomas to suppress growth by targeting the IGF-1R oncogene and that miR-181b may serve as a novel therapeutic target for gliomas.
RNA 02/2013; · 5.09 Impact Factor
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Ying-Yi Wang,
Guan Sun,
Hui Luo, Xie-Feng Wang,
Feng-Ming Lan,
Xiao Yue,
Lin-Shan Fu,
Pei-Yu Pu,
Chun-Sheng Kang,
Ning Liu,
Yong-Ping You
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ABSTRACT: As an important oncogenic miRNA, miR-21 has been reported to play crucial roles in glioblastoma (GBM) carcinogenesis. However, the precise biological function and molecular mechanism of miR-21 in GBM remain elusive. This study is designed to explore the mechanism of miR-21 involved in the control of GBM cell growth.
MTT assay, cell cycle analysis, and apoptosis analysis showed that reduction of miR-21 inhibited cell growth in U87 and LN229 GBM cells. Further, reduction of miR-21 decreased the expression of human telomerase reverse transcriptase (hTERT) and repressed STAT3 expression and STAT3 phosphorylation. STAT3 inhibition led to a remarkable depletion of hTERT at both mRNA and protein levels by binding to the hTERT gene promoter by performing luciferase reporter assay and chromatin Immunoprecipitation PCR. Finally, knockdown of miR-21 considerably inhibited tumor growth and diminished the expression of STAT3 and hTERT in xenograft model.
Our findings indicate that miR-21 regulates hTERT expression mediated by STAT3, therefore controlling GBM cell growth.
CNS Neuroscience & Therapeutics 06/2012; 18(9):722-8. · 4.44 Impact Factor
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ABSTRACT: To study the expression of RAS protein in human glioma tissues and its influence on tumor growth.
RAS protein expression in glioma tissues was determined by immunohistochemical (IHC) staining. Subsequently, MTT cell proliferation assay, flow cytometry and Western blotting were used to assay U251 cells with reduced RAS expression.
The expression of RAS in glioma was increased and strongly correlated with pathological grade. Downregulation of RAS resulted in glioma cells growth suppression and increased apoptosis.
The expression level of RAS protein in human glioma was increased. Downregulation of RAS can inhibit glioblastoma cell growth through the RAS signal pathway.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 04/2012; 29(2):159-62.
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Zhu-mei Shi,
Jing Wang,
Zhiping Yan,
Yong-ping You,
Chong-yong Li,
Xu Qian,
Yu Yin,
Peng Zhao,
Ying-ying Wang, Xie-feng Wang,
Ming-na Li,
Ling-Zhi Liu,
Ning Liu,
Bing-Hua Jiang
[show abstract]
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ABSTRACT: MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators through targeting mRNAs for translational repression or degradation. In this study, we showed that miR-128 expression levels were decreased in glioma, and identified p70S6K1 as a novel direct target of miR-128. Overexpression of miR-128 suppressed p70S6K1 and its downstream signaling molecules such as HIF-1 and VEGF expression, and attenuated cell proliferation, tumor growth and angiogenesis. Forced expression of p70S6K1 can partly rescue the inhibitory effect of miR-128 in the cells. Taken together, these findings will shed light to the role and mechanism of miR-128 in regulating glioma tumor angiogenesis via miR-128/p70S6K1 axis, and miR-128 may serve as a potential therapeutic target in glioma in the future.
PLoS ONE 01/2012; 7(3):e32709. · 4.09 Impact Factor
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Xie-Feng Wang,
Zhu-Mei Shi,
Xi-Rui Wang,
Lei Cao,
Ying-Yi Wang,
Jun-Xia Zhang,
Yu Yin,
Hui Luo,
Chun-Sheng Kang,
Ning Liu,
Tao Jiang,
Yong-Ping You
[show abstract]
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ABSTRACT: Recently, several microRNAs (miRNAs) were reported to be involved in the modulation of glioma development. The aim of our study was to determine the effect of miR-181d on the growth of glioma and to investigate whether this growth is modulated by targeting K-ras and Bcl-2.
Real-time PCR was used to analyze the expression of miR-181d in human glioma samples and glioma cell lines. Apoptosis, cell cycle, and proliferation (MTT) assays were performed to assess the phenotypic changes in glioma cells. Immunohistochemistry was used to determine the expression of K-ras and Bcl-2 in glioma tissues, and a luciferase reporter assay was carried out to confirm whether K-ras and Bcl-2 are direct targets of miR-181d. Western blotting was used to identify the potential signaling pathways affected glioma cell growth by miR-181d. In vivo, xenograft tumors were examined for an anti-glioma effect of miR-181d.
MiR-181d was down-regulated in human glioma samples and up-regulated in transfected glioma cells. Ectopic expression of miR-181d suppressed proliferation and triggered cell cycle arrest and apoptosis in glioma cell lines. K-ras and Bcl-2 were identified as direct targets of miR-181d and were up-regulated in glioma samples. The results showed evidence linking the tumor suppressor activity of miR-181d in glioma cells with the K-ras-related PI3K/AKT and MAPK/ERK pathways. Furthermore, xenograft tumors from miR-181d-treated U251 cells were suppressed in vivo.
MiR-181d may act as a glioma suppressor by targeting K-ras and Bcl-2.
Journal of Cancer Research and Clinical Oncology 12/2011; 138(4):573-84. · 2.56 Impact Factor
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De-gang Wu,
Ying-yi Wang,
Li-gang Fan,
Hui Luo,
Bin Han,
Li-hua Sun, Xie-feng Wang,
Jun-xia Zhang,
Lei Cao,
Xi-rui Wang,
Yong-ping You,
Ning Liu
[show abstract]
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ABSTRACT: Invasion growth is the most characteristic biological phenotype of glioblastoma, but the molecular mechanism in glioma cell invasion is poorly understood. Recent data have showed that microRNA plays an essential role in tumor invasion. Our study aimed to explore the mechanism of miR-7 involved in the control of glioblastoma cell invasion.
Glioma cell invasion was evaluated by transwell and scratch assays after up-regulation of miR-7 using miR-7 mimics in U87 and U251 cells. Luciferase reporter assay was used to determine focal adhesion kinase (FAK) as a target of miR-7. The levels of miR-7, matrix metalloproteinases (MMP)-2 and MMP-9 mRNA were detected by PCR assay, and the levels of FAK, MMP-2, MMP-9, total and phosphorylation serine/threonine kinase (AKT), and extracellular signal-regulated kinase (ERK) 1/2 were measured by Western blotting analysis.
Over-expression of miR-7 inhibited the invasion and migration activity of U87 and U251 cells. And up-regulation of miR-7 reduced FAK protein expression, Further, luciferase reporter assay showed that miR-7 modulated FAK expression directly by binding 3'UTR of FAK mRNA. In addition, miR-7 repressed p-ERK1/2 and p-AKT level, MMP-2 and MMP-9 expression. Finally, the inverse relationship between FAK and miR-7 expression was certificated in human glioma tissues.
To our knowledge, these data indicate for the first time that miR-7 directly regulates cell invasion by targeting FAK in glioblastoma and that miR-7 could be a potential therapeutic target for glioblastoma intervention.
Chinese medical journal 09/2011; 124(17):2616-21. · 0.86 Impact Factor
