hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells

Shi, Lei; Cheng, Zihao; Zhang, Junxia; Li, Rui; Zhao, Peng; Fu, Zhen-Yan; You, Yongping

doi:10.1016/j.brainres.2008.07.085

Cited by 393 publications

(326 citation statements)

References 23 publications

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“…miR-181a was proven to be related to certain type of cancers (19). However, the clinical relevance and function of miR-181a in GBM remains elusive.…”

Section: Discussionmentioning

confidence: 99%

The correlation of microRNA-181a and target genes with poor prognosis of glioblastoma patients

Huang¹,

Zhao²,

Weng³

et al. 2016

International Journal of Oncology

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Abstract. To investigate the expression and clinical significance of miR-181a and its target genes in glioblastoma multiforme (GBM), the expression levels of miR-181a and three target genes in human normal brain tissues and GBM were analyzed in silico using gene microarray, Gene Ontology, KEGG pathway and hierarchical clustering analysis followed by validation with quantitative RT-PCR. Our results show that miR-181a is down-regulated in GBM patients. The three target genes, ANGPT2, ARHGAP18 and LAMC1, are negatively correlated with the expression of miR-181a. Moreover, high expression of ANGPT2 or LAMC1 together with large size of GBM is correlated with a shorter median overall survival. In conclusion, our results showed that miR-181a and it targets ANGPT2 and LAMC1 might be predictors of prognosis in GBM patients.

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“…miR-181a was proven to be related to certain type of cancers (19). However, the clinical relevance and function of miR-181a in GBM remains elusive.…”

Section: Discussionmentioning

confidence: 99%

The correlation of microRNA-181a and target genes with poor prognosis of glioblastoma patients

Huang¹,

Zhao²,

Weng³

et al. 2016

International Journal of Oncology

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“…Many studies have investigated the function of miR-181a in tissues where it is highly expressed, such as thymus, brain and spleen [35,36]. It has also been reported that miR-181a is a critical player in epithelial cell adhesion molecule (EpCAM)-positive hepatic cancer stem cells by targeting transcriptional regulators of differentiation [37].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR-181a upregulates sirtuin-1 (SIRT1) and improves hepatic insulin sensitivity

et al. 2012

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Aims/hypothesis Sirtuin-1 (SIRT1) is a potential therapeutic target to combat insulin resistance and type 2 diabetes. This study aims to identify a microRNA (miRNA) targeting SIRT1 to regulate hepatic insulin sensitivity. Methods Luciferase assay combined with mutation and immunoblotting was used to screen and verify the bioinformatically predicted miRNAs. miRNA and mRNA levels were measured by real-time PCR. Insulin signalling was detected by immunoblotting and glycogen synthesis. Involvement of SIRT1 was studied with adenovirus, inhibitor and SIRT1-deficient hepatocytes. The role of miR-181a in vivo was explored with adenovirus and locked nucleic acid antisense oligonucleotides. Results miR-181a targets the 3′ untranslated region (3′UTR) of Sirt1 mRNA through a miR-181a binding site, and downregulates SIRT1 protein abundance at the translational level. miR-181a is increased in insulin-resistant cultured hepatocytes and liver, and in the serum of diabetic patients. Overexpression of miR-181a decreases SIRT1 protein levels and activity, and causes insulin resistance in hepatic cells. Inhibition of miR-181a by antisense oligonucleotides increases SIRT1 protein levels and activity, and improves insulin sensitivity in hepatocytes. Ectopic expression of SIRT1 abrogates the effect of miR-181a on insulin sensitivity, and inhibition of SIRT1 activity or SIRT1 deficiency markedly attenuated the improvement in insulin sensitivity induced by antisense miR-181a. In addition, overexpression of miR181a by adenovirus impairs hepatic insulin signalling, and intraperitoneal injection of locked nucleic acid antisense oligonucleotides for miR-181a improves glucose homeostasis in diet-induced obesity mice. Conclusions/interpretation miR-181a regulates SIRT1 and improves hepatic insulin sensitivity. Inhibition of miR-181a might be a potential new strategy for treating insulin resistance and type 2 diabetes.

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“…10,26,27 However, another study found that it functioned as a tumor suppressor in human glioma cells. 28 The reason for this was that certain miRNA may be oncogenic in one cell or tissue type but tumor suppressive in another, depending on the cancer type and cellular context. 29 Further, we showed that overexpression of miR-181a typically reduced the basal TEER value, indicating a key role of miR-181a in regulating BTB integrity.…”

Section: Discussionmentioning

confidence: 99%

MiR-181a Regulates Blood-Tumor Barrier Permeability by Targeting Krüppel-Like Factor 6

Yao

Wang

et al. 2014

J Cereb Blood Flow Metab

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Blood-tumor barrier (BTB) constitutes an efficient organization of tight junctions that impairs the delivery of therapeutic drugs. However, the methods and molecular mechanisms underlying the BTB opening remain elusive. MicroRNAs (miRNAs) have recently emerged as key regulators of various biologic processes and therapeutic targets. In this study, we have identified microRNA-181a (miR-181a) as a critical miRNA in opening BTB. MicroRNA-181a expression was upregulated in glioma endothelial cells (GECs), which were obtained by coculturing endothelial cells (ECs) with glioma cells. Overexpression of miR-181a resulted in an impaired and permeability increased BTB, and meanwhile reduced the expression of zonula occluden (ZO)-1, occludin, and claudin-5. Kruppel-like factor 6 (KLF6), a transcription factor of the zinc-finger family, was downregulated in GECs. Mechanistic investigations defined it as a direct and functional downstream target of miR-181a, which was involved in the regulation of BTB permeability and the expression of ZO-1, occludin, and claudin-5. Furthermore, luciferase assays and chromatin immunoprecipitation assays showed that KLF6 upregulated the promoter activities and interacted with the promoters of ZO-1, occludin, and claudin-5 in GECs. Collectively, we showed the possibility that overexpression of miR-181a contributes to the increased permeability of BTB by targeting KLF6, thereby revealing potential therapeutic targets for the treatment of brain gliomas.

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hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells

Cited by 393 publications

References 23 publications

The correlation of microRNA-181a and target genes with poor prognosis of glioblastoma patients

The correlation of microRNA-181a and target genes with poor prognosis of glioblastoma patients

Downregulation of miR-181a upregulates sirtuin-1 (SIRT1) and improves hepatic insulin sensitivity

MiR-181a Regulates Blood-Tumor Barrier Permeability by Targeting Krüppel-Like Factor 6

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