MIR-451 and Imatinib mesylate inhibit tumor growth of Glioblastoma stem cells

Gal, Hilah; Pandi, Gopal; Kanner, Andrew A.; Ram, Zvi; Lithwick‐Yanai, Gila; Amariglio, Ninette; Rechavi, Gideon; Givol, David

doi:10.1016/j.bbrc.2008.08.107

Cited by 220 publications

(156 citation statements)

References 19 publications

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“…Moreover, overexpression of these miRNAs in GSCs suppresses proliferation and induces differentiation of GSCs, indicating that these miRNAs have important roles in maintaining a GSC phenotype. Further, external expression of miR-451 disrupts tumorsphere formation and suppresses tumor growth of GSCs in vivo, suggesting a tumor suppressor role of miR-451 in GBMs (Gal et al, 2008). These studies indicate that some critical miRNAs can be potentially used as molecular targets or therapeutic agents for targeting GSCs.…”

Section: Regulation Of Glioblastoma Stem Cells By Micro Rnasmentioning

confidence: 76%

“…However, levels of miR-124, miR-137 and miR-451 are significantly reduced in malignant gliomas (both grade III and grade IV) relative to normal brain (Silber et al, 2008;Gal et al, 2008). The roles of miRNAs in GSCs have been demonstrated in two recent studies showing that miR-124, miR-137 and miR-451 levels are significantly reduced in GSCs relative to non-stem tumor cells (Silber et al, 2008;Gal et al, 2008). Moreover, overexpression of these miRNAs in GSCs suppresses proliferation and induces differentiation of GSCs, indicating that these miRNAs have important roles in maintaining a GSC phenotype.…”

Section: Regulation Of Glioblastoma Stem Cells By Micro Rnasmentioning

confidence: 98%

“…For example, miRNA-21 is overexpressed in GBM tumors and functional blockade of this miRNA induces apoptotic cell death (Conti et al, 2009). However, levels of miR-124, miR-137 and miR-451 are significantly reduced in malignant gliomas (both grade III and grade IV) relative to normal brain (Silber et al, 2008;Gal et al, 2008). The roles of miRNAs in GSCs have been demonstrated in two recent studies showing that miR-124, miR-137 and miR-451 levels are significantly reduced in GSCs relative to non-stem tumor cells (Silber et al, 2008;Gal et al, 2008).…”

Section: Regulation Of Glioblastoma Stem Cells By Micro Rnasmentioning

confidence: 99%

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Cancer stem cells in glioblastoma—molecular signaling and therapeutic targeting

et al. 2010

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Glioblastomas (GBMs) are highly lethal primary brain tumors. Despite current therapeutic advances in other solid cancers, the treatment of these malignant gliomas remains essentially palliative. GBMs are extremely resistant to conventional radiation and chemotherapies. We and others have demonstrated that a highly tumorigenic subpopulation of cancer cells called GBM stem cells (GSCs) promotes therapeutic resistance. We also found that GSCs stimulate tumor angiogenesis by expressing elevated levels of VEGF and contribute to tumor growth, which has been translated into a useful therapeutic strategy in the treatment of recurrent or progressive GBMs. Furthermore, stem cell-like cancer cells (cancer stem cells) have been shown to promote metastasis. Although GBMs rarely metastasize beyond the central nervous system, these highly infiltrative cancers often invade into normal brain tissues preventing surgical resection, and GSCs display an aggressive invasive phenotype. These studies suggest that targeting GSCs may effectively reduce tumor recurrence and significantly improve GBM treatment. Recent studies indicate that cancer stem cells share core signaling pathways with normal somatic or embryonic stem cells, but also display critical distinctions that provide important clues into useful therapeutic targets. In this review, we summarize the current understanding and advances in glioma stem cell research, and discuss potential targeting strategies for future development of anti-GSC therapies.

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Section: Regulation Of Glioblastoma Stem Cells By Micro Rnasmentioning

confidence: 76%

Section: Regulation Of Glioblastoma Stem Cells By Micro Rnasmentioning

confidence: 98%

Section: Regulation Of Glioblastoma Stem Cells By Micro Rnasmentioning

confidence: 99%

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Cancer stem cells in glioblastoma—molecular signaling and therapeutic targeting

et al. 2010

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“…miR-221 and miR-222 were shown to be highly expressed in GBIV relative to adjacent the normal brain tissue and to be involved in regulation of cell cycle checkpoints (Gillies and Lorimer, 2007;Medina et al, 2008;Conti et al, 2009). The expression of miR-124, miR-137, miR-146b, miR-7, miR-181, miR-128 and miR-451 was found to be lower in GBIV compared with the non-neoplastic brain and inhibitors of glioma cell growth (Gal et al, 2008;Godlewski et al, 2008;Kefas et al, 2008;Shi et al, 2008;Silber et al, 2008;Xia et al, 2009).…”

Section: Introductionmentioning

confidence: 97%

De-repression of CTGF via the miR-17-92 cluster upon differentiation of human glioblastoma spheroid cultures

et al. 2010

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All-trans retinoic acid is a potent promoter of cellular differentiation processes, which is used in cancer therapy. Glioblastoma spheroid cultures are enriched in tumorinitiating cells, and provide a model to test new treatment options in vitro. We investigated the molecular mechanisms of response to exposure to differentiation-promoting conditions in such cultures. Microarray analyses of five independent cultures showed that after induction of differentiation, inhibitors of transforming growth factorb/bone morphogenetic protein, Wnt/b-catenin and IGF signaling were upregulated, whereas expression of several microRNAs decreased, particularly that of the miR-17-92 cluster. In primary astrocytic gliomas (n ¼ 82), expression of several members of miR-17-92 was significantly higher relative to those of normal brain (n ¼ 8) and significantly increased with tumor grade progression (Po0.05). A high-level amplification of the miR-17-92 locus was detected in one glioblastoma specimen. Transfection of inhibitors of miR-17-92 induced increased apoptosis and decreased cell proliferation in glioblastoma spheroids. Mir-17-92 inhibition was also associated with increased messenger RNA (mRNA) and/or protein expression of CDKN1A, E2F1, PTEN and CTGF. The CTGF gene was shown to be a target of miR-17-92 in glioblastoma spheroids by luciferase reporter assays. Our results suggest that miR-17-92 and its target CTGF mediate effects of differentiation-promoting treatment on glioblastoma cells through multiple regulatory pathways.

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“…Early studies have also highlighted the roles of miR-144/451 in human cancers. Many studies have established that miR-451 is widely dysregulated in human malignancies, including in lung cancer (14,15), gastric cancer (16), breast cancer (17,18), glioma (19)(20)(21), and leukemia (22), indicating that miR-451 might play a critical role in oncogenesis. In this review, we focus on the noncanonical biogenesis pathway for miR-451 and its roles in erythroid differentiation.…”

Section: Introductionmentioning

confidence: 99%

The Potential Role of miR-451 in Cancer Diagnosis, Prognosis, and Therapy

Pan

Wang

2013

Molecular Cancer Therapeutics

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MicroRNAs (miRNA) are small noncoding RNAs that converge to maintain an intrinsic balance of various processes, including cell proliferation, differentiation, and apoptosis. Recent research efforts have been devoted to translating these basic discoveries into applications that could improve the early diagnosis and therapeutic outcome of patients with cancer. Early studies have shown that miRNA-451 (miR-451) is widely dysregulated in human cancers and plays a critical role in tumorigenesis and tumor progression. In this review, we summarize the potential use of miR-451 for cancer diagnosis, prognosis, and treatment. In addition, we discuss the possible mechanisms of miR-451 dysregulation and future challenges in development of miR-451 as a noninvasive biomarker and a potential therapeutic target in human cancers.

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MIR-451 and Imatinib mesylate inhibit tumor growth of Glioblastoma stem cells

Cited by 220 publications

References 19 publications

Cancer stem cells in glioblastoma—molecular signaling and therapeutic targeting

Cancer stem cells in glioblastoma—molecular signaling and therapeutic targeting

De-repression of CTGF via the miR-17-92 cluster upon differentiation of human glioblastoma spheroid cultures

The Potential Role of miR-451 in Cancer Diagnosis, Prognosis, and Therapy

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