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Zhang J.,Tianjin Medical University | Zhang J.,Tianjin Neurological Institute | Zhang J.,Nanjing Medical University | Han L.,Tianjin Neurological Institute | And 14 more authors.
International Journal of Oncology | Year: 2010

MicroRNAs (miRNAs) are short regulatory RNAs that negatively modulate protein expression at a post-transcriptional level. Emerging evidence suggests that miRNAs play important roles in the pathogenesis of several types of cancers. However, the further mechanisms of miRNA remain unknown. In this study, we aimed to explore the coordinated function of miR-221/222 in glioma by bioinformatics and experiment methods. Bioinformatics analysis revealed that miR-221/222 had the potential to regulate about 70 common target genes and may exert a cooperative effect on regulation and function via Akt signaling pathway. Overexpression of miR-221/222 increased glioma cell proliferation and invasion in vitro and induced glioma growth in a subcutaneous mouse model. Furthermore, miR-221/222 overexpression resulted in an obvious activation of p-Akt and significant changes of Akt-related gene expression in glioma cells. Our results suggest that miR-221/222 co-enhance the glioma malignant phenotype via activation of the Akt pathway mediated by regulation of common gene expression.

Zhang J.,Tianjin Medical University | Zhang J.,Tianjin Key Laboratory of Nerve Injury | Zhang A.,Tianjin Medical University | Zhang A.,Tianjin Key Laboratory of Nerve Injury | And 7 more authors.
Future Oncology | Year: 2012

STAT3 signaling has been linked to the development of various cancers and is widely recognized as a critical molecular target for cancer therapy. ncRNAs, especially miRNAs and lncRNAs, are acting as promising biomarkers and therapy targets implicated in tumor pathogenesis. This review focuses on the most up-to-date knowledge of miRNAs and lncRNAs, and their involvement with STAT3 signaling. The important miRNAs involved in the STAT3 pathway are summarized in a complex interaction network. The lncRNAs' potential for targeting STAT3 at post-transcriptional level was predicted based upon lncRNA-mRNA interaction. The current and potential STAT3-targeted therapeutics are also discussed. © 2012 Future Medicine Ltd.

Zhang C.-Z.,Tianjin Medical University | Zhang C.-Z.,Tianjin Huanhu hospital | Zhang J.-X.,Tianjin Medical University | Zhang A.-L.,Tianjin Medical University | And 13 more authors.
Molecular Cancer | Year: 2010

Background: MiR-221 and miR-222 (miR-221/222) are frequently up-regulated in various types of human malignancy including glioblastoma. Recent studies have reported that miR-221/222 regulate cell growth and cell cycle progression by targeting p27 and p57. However the underlying mechanism involved in cell survival modulation of miR-221/222 remains elusive.Results: Here we showed that miR-221/222 inhibited cell apoptosis by targeting pro-apoptotic gene PUMA in human glioma cells. Enforced expression of miR-22/222 induced cell survival whereas knockdown of miR-221/222 rendered cells to apoptosis. Further, miR-221/222 reduced PUMA protein levels by targeting PUMA-3'UTR. Introducing PUMA cDNA without 3'UTR abrogated miR-221/222-induced cell survival. Notably, knockdown of miR-221/222 induces PUMA expression and cell apoptosis and considerably decreases tumor growth in xenograft model. Finally, there was an inverse relationship between PUMA and miR-221/222 expression in glioma tissues.Conclusion: To our knowledge, these data indicate for the first time that miR-221/222 directly regulate apoptosis by targeting PUMA in glioblastoma and that miR-221/222 could be potential therapeutic targets for glioblastoma intervention. © 2010 Zhang et al; licensee BioMed Central Ltd.

Han L.,Tianjin Neurological Institute | Han L.,Tianjin Medical University | Zhang A.,Tianjin Neurological Institute | Zhang A.,Tianjin Medical University | And 9 more authors.
International Journal of Oncology | Year: 2010

miRNAs are non-coding, single-stranded RNAs that regulate target gene expression by repressing translation or promoting RNA cleavage. Dicer is an essential component of the miRNA processing machinery. To identify a role for miRNAs in tumorigenesis, we designed an adenovirus expressing small hairpin RNA (shRNA) to silence Dicer and globally suppress the maturation of miRNAs. We identified that the impairment of miRNA processing conferred an enhanced proliferative activity and invasive ability on each of three tumor cell lines in vitro. Inhibition of Dicer was associated with activation of p-AKT and enhanced expression of the cell cycle associating molecules, cyclin A and PCNA, as well as MMP-2 and MMP-9, proteins involved in tumor cell invasion. Adenoviral gene silencing of Dicer in subcutaneous MCF-7 xenografts significantly increased tumor growth in vivo compared to tumors infected with non-loading adenovirus. Increased tumor growth was associated with p-AKT activation and upregulation of cyclin A, PCNA MMP-2 and MMP-9. These findings demonstrate that global reduction of miRNA processing by silencing Dicer enhances tumor proliferation and invasion, and the p-AKT pathway may contribute to this phenotype via the downstream molecules, cyclin A, PCNA, MMP-2 and MMP-9.

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