microRNA-7 Inhibits the Epidermal Growth Factor Receptor and the Akt Pathway and Is Down-regulated in Glioblastoma

Edited by Tamas DalmayKeyword: miR-483-5p cell proliferation ERK1 glioma a b s t r a c t MicroRNAs (miRNAs) exhibit tumor-specific expression signatures and play crucial roles in tumorigenesis by targeting oncogenes. Here, through analyzing the miRNA-array profiles of human glioblastoma tissues and the adjacent normal brain tissues, we found miR-483-5p was significantly down-regulated in gliomas, which was confirmed in both human glioma specimens and cell lines. The overexpression of miR-483-5p suppressed glioma cell proliferation and induced a G0/G1 arrest. In contrast, miR-483-5p inhibition promoted cell proliferation. Furthermore, by a dual-luciferase reporter assay and expression analysis, we identified extracellular signal-regulated kinase 1 (ERK1) as a direct target of miR-483-5p. ERK1 knockdown can block cell proliferation induced by miR-483-5p inhibition. Thus, our findings provide the first evidence that miR-483-5p can serve as a tumor suppressor in gliomas.

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“…MiR-7, expressing at a low level in glioblastoma [12], was used as a positive control for miRNA specificity. As shown in Fig.…”

Section: The Expression Of Mir-483-5p Is Decreased In Glioma Tissues mentioning

confidence: 99%

MiR‐483–5p suppresses the proliferation of glioma cells via directly targeting ERK1

et al. 2012

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“…In addition, it still positively regulates miR-7 (Reddy et al, 2008), which was found to control epidermal growth factor receptor signaling and promote photoreceptor differentiation, inducing cell cycle arrest and cell death in some cancer cell lines (Kefas et al, 2008;Webster et al, 2009). miRNA expression profiling revealed that miR-7 was involved in tumor aggressiveness, invasion and metastasis in urothelial carcinomas and breast cancer (Foekens et al, 2008;Veerla et al, 2009).…”

Section: Pro-metastatic Mirnas Regulate Tumor Metastasismentioning

confidence: 99%

The microRNA network and tumor metastasis

2009

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Metastasis is the most significant process affecting the clinical management of cancer patients and occurs in multiple sequential steps. However, the molecular pathways underlying each step still remain obscure. Recent research has shown that there is a microRNA (miRNA) network that functions as a regulator of tumor metastasis. In this paper, we review the role of miRNAs in tumor metastasis, including control of epithelial-mesenchymal transition, regulation of metastasis-associated genes and epigenetic alterations. More information on miRNAs will promote a better understanding of the molecular mechanism of metastasis.

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“…miR‐7, which acts as a tumor suppressor, directly targets EGFR and can independently repress the Akt pathway through targeting of its upstream regulators. In GBM, miR‐7 is frequently downregulated, allowing for enhanced activation of the Akt pathway, and thus increased viability and invasiveness of tumor cells 23, 24. These protumorigenic effects can be corrected with transfection of mimic miR‐7 oligonucleotides, which results in decreased invasiveness and increased apoptosis of GBM cell lines 23, 24.…”

Section: Introductionmentioning

confidence: 99%

“…miR‐7 also has many targets involved in metastasis including FAK, PI3K, EGFR, and RAF1 23, 24, 75, 76. As indicated by its targets, miR‐7 functions as a tumor suppressor and is downregulated in GBM.…”

Section: Introductionmentioning

confidence: 99%

“…Its overexpression can inhibit metastasis and invasion of GBM cells by directly repressing FAK , a mediator of cell‐extracellular matrix signaling, as well as by reducing the expression of MMP2 and MMP9 , thereby decreasing the ability of GBM cells to move through extracellular matrix 75. Further, by suppressing EGFR expression and inhibiting the Akt pathway, miR‐7 can decrease the viability and invasiveness of GBM cells 23.…”

Section: Introductionmentioning

confidence: 99%

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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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microRNA-7 Inhibits the Epidermal Growth Factor Receptor and the Akt Pathway and Is Down-regulated in Glioblastoma

Cited by 675 publications

References 19 publications

MiR‐483–5p suppresses the proliferation of glioma cells via directly targeting ERK1

MiR‐483–5p suppresses the proliferation of glioma cells via directly targeting ERK1

The microRNA network and tumor metastasis

MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics

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