miR-182 as a Prognostic Marker for Glioma Progression and Patient Survival

Jiang, Lili; Mao, Pu; Song, Libing; Wu, Jueheng; Huang, Jieting; Lin, Chuyong; Yuan, Jie; Qu, Liang‐Hu; Cheng, Shi Yuan; Li, Jun

doi:10.2353/ajpath.2010.090812

Cited by 148 publications

(118 citation statements)

References 42 publications

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“…Our previous microarray analysis showed that miR-486 is substantially overexpressed in gliomas [28]. Consistently, real-time PCR analysis revealed that miR-486 was markedly overexpressed in 8 primary glioma tissues compared with the paired tumor-adjacent brain tissues, as well as in all 14 tested glioma cell lines compared with NHA ( Figure 5A and 5B).…”

Section: Mir-486 Overexpression Correlates With Progression Of Human supporting

confidence: 52%

“…Analysis using publicly available algorithms (TargetScan, Pictar, miRANDA) showed that Cezanne is the predicted target of miR-486 (Figure 2A), a miRNA that has been found to be substantially overexpressed in gliomas [28]. To investigate the effect of miR-486 on Cezanne expression and its biological role in gliomas progression, U87MG and SNB19 glioma cells were engineered to stably overexpress miR-486 ( Figure 2B).…”

Section: Mir-486 Targets and Suppresses Cezannementioning

confidence: 99%

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miR-486 sustains NF-κB activity by disrupting multiple NF-κB-negative feedback loops

Song

Lin²,

Gong³

et al. 2012

Cell Res

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Deubiquitinases, such as CYLD, A20 and Cezanne, have emerged as important negative regulators that balance the strength and the duration of NF-κB signaling through feedback mechanisms. However, how these serial feedback loops are simultaneously disrupted in cancers, which commonly exhibit constitutively activated NF-κB, remains puzzling. Herein, we report that miR-486 directly suppresses NF-κB-negative regulators, CYLD and Cezanne, as well as multiple A20 activity regulators, including ITCH, TNIP-1, TNIP-2 and TNIP-3, resulting in promotion of ubiquitin conjugations in NF-κB signaling and sustained NF-κB activity. Furthermore, we demonstrate that upregulation of miR-486 promotes glioma aggressiveness both in vitro and in vivo through activation of NF-κB signaling pathway. Importantly, miR-486 levels in primary gliomas significantly correlate with NF-κB activation status. These findings uncover a novel mechanism for constitutive NF-κB activation in gliomas and support a functionally and clinically relevant epigenetic mechanism in cancer progression.

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Section: Mir-486 Overexpression Correlates With Progression Of Human supporting

confidence: 52%

Section: Mir-486 Targets and Suppresses Cezannementioning

confidence: 99%

miR-486 sustains NF-κB activity by disrupting multiple NF-κB-negative feedback loops

Song

Lin²,

Gong³

et al. 2012

Cell Res

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“…In addition to our human tissue studies showing that miR-182 is upregulated in a subset of malignant melanomas (Segura et al, 2009), this miRNA has also been found to be a prognostic marker for glioma progression (Jiang et al, 2010), and to be highly expressed in colon (Bandres et al, 2007) and breast cancer cell lines (Guttilla and White, 2009). Therefore, anti-miR-182 may have additional antitumoral applications beyond melanoma.…”

Section: Targeting Liver Metastasis With Anti-mir-182mentioning

confidence: 58%

Efficient in vivo microRNA targeting of liver metastasis

et al. 2010

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Targeting oncogenic microRNAs (miRNAs) is emerging as a promising strategy for cancer therapy. In this study, we provide proof of principle for the safety and efficacy of miRNA targeting against metastatic tumors. We tested the impact of targeting miR-182, a pro-metastatic miRNA frequently overexpressed in melanoma, the in vitro silencing of which represses invasion and induces apoptosis. Specifically, we assessed the effect of anti-miR-182 oligonucleotides synthesized with 2 0 sugar modifications and a phosphorothioate backbone in a mouse model of melanoma liver metastasis. Luciferase imaging showed that mice treated with anti-miR-182 had a lower burden of liver metastases compared with control. We confirmed that miR-182 levels were effectively downregulated in the tumors of anti-miR-treated mice compared with tumors of control-treated mice, both in the liver and in the spleen. This effect was accompanied by an upregulation of multiple miR-182 direct targets. Transcriptional profiling of tumors treated with anti-miR-182 or with control oligonucleotides revealed an enrichment of genes controlling survival, adhesion and migration modulated in response to anti-miR-182 treatment. These data indicate that in vivo administration of anti-miRs allows for efficient miRNA targeting and concomitant upregulation of miRNAcontrolled genes. Our results demonstrate that the use of anti-miR-182 is a promising therapeutic strategy for metastatic melanoma and provide a solid basis for testing similar strategies in human metastatic tumors.

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“…The signature included three miRNAs (miR‐20a, miR‐106a, and miR‐17‐5p) that were protective and seven (miR‐31, miR‐222, miR‐148a, miR‐221, miR‐146b, miR‐200b, and miR‐193a) that were risky with respect to the association between their expression and patient survival. Additionally, other studies have found that high expression of miR‐21, miR‐182, and miR‐196 as well as low expression of miR‐181b and miR‐106a are associated with poor patient outcomes 19, 85, 86.…”

Section: Introductionmentioning

confidence: 97%

“…18 identified 12 miRNAs (miR‐9, miR‐15a, miR‐16, miR‐17, miR‐19a, miR‐20a, miR‐21, miR‐25, miR‐28, miR‐130b, miR‐140, and miR‐210) that were upregulated and two (miR‐184 and miR‐328) that were downregulated during progression 18. Other studies have additionally found miRNAs that are differentially expressed in advanced clinical stages of GBM, including miR‐182, which is upregulated and miR‐137, which is downregulated in late stages 19, 20.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics

Harish²,

et al. 2016

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Glioblastoma multiforme (GBM) is the most common and lethal cancer of the adult brain, remaining incurable with a median survival time of only 15 months. In an effort to identify new targets for GBM diagnostics and therapeutics, recent studies have focused on molecular phenotyping of GBM subtypes. This has resulted in mounting interest in microRNAs (miRNAs) due to their regulatory capacities in both normal development and in pathological conditions such as cancer. miRNAs have a wide range of targets, allowing them to modulate many pathways critical to cancer progression, including proliferation, cell death, metastasis, angiogenesis, and drug resistance. This review explores our current understanding of miRNAs that are differentially modulated and pathologically involved in GBM as well as the current state of miRNA‐based therapeutics. As the role of miRNAs in GBM becomes more well understood and novel delivery methods are developed and optimized, miRNA‐based therapies could provide a critical step forward in cancer treatment.

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miR-182 as a Prognostic Marker for Glioma Progression and Patient Survival

Cited by 148 publications

References 42 publications

miR-486 sustains NF-κB activity by disrupting multiple NF-κB-negative feedback loops

miR-486 sustains NF-κB activity by disrupting multiple NF-κB-negative feedback loops

Efficient in vivo microRNA targeting of liver metastasis

MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics

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