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miR-93 promotes cell proliferation in gliomas through activation of PI3K/Akt signaling pathway.

Jiang L, Wang C, Lei F, Zhang L, Zhang X, Liu A, Wu G, Zhu J, Song L - Oncotarget (2015)

Bottom Line: Multiple regulators, such as phosphatase and tensin homolog (PTEN) and PH domain leucine rich repeat protein phosphatases (PHLPP), have also found to be involved in suppression of the PI3K/Akt signaling pathway.Furthermore, we found that overexpressing miR-93 promoted, but inhibition of miR-93 reduced, glioma cell proliferation and cell-cycle progression.Therefore, our results suggest that miR-93 might play an important role in glioma progression and uncover a novel mechanism for constitutive PI3K/Akt activation in gliomas.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, Guangzhou Medical University, Guangzhou 510182, China.

ABSTRACT
The PI3K/Akt signaling pathway is frequently activated in various human cancer types and plays essential roles in development and progression of cancers. Multiple regulators, such as phosphatase and tensin homolog (PTEN) and PH domain leucine rich repeat protein phosphatases (PHLPP), have also found to be involved in suppression of the PI3K/Akt signaling pathway. However, how suppressive effects mediated by these regulators are concomitantly disrupted in cancers, which display constitutively activated PI3K/Akt signaling, remains puzzling. In the present study, we reported that the expression of miR-93 was markedly upregulated in glioma cell lines and clinical glioma tissues. Statistical analysis revealed that miR-93 levels significantly correlated with clinicopathologic grade and overall survival in gliomas. Furthermore, we found that overexpressing miR-93 promoted, but inhibition of miR-93 reduced, glioma cell proliferation and cell-cycle progression. We demonstrated that miR-93 activated PI3K/Akt signaling through directly suppressing PTEN, PHLPP2 and FOXO3 expression via targeting their 3'UTRs. Therefore, our results suggest that miR-93 might play an important role in glioma progression and uncover a novel mechanism for constitutive PI3K/Akt activation in gliomas.

No MeSH data available.


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The model of miR-93-mediated PI3K/Akt signaling activation via down-regulation of PTEN, PHLPP2 and FOXO3 that results in the promotion of cell proliferation in gliomas
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Figure 7: The model of miR-93-mediated PI3K/Akt signaling activation via down-regulation of PTEN, PHLPP2 and FOXO3 that results in the promotion of cell proliferation in gliomas

Mentions: Numerous studies have demonstrated that activation of the PI3K/Akt signaling pathway is essential to the development and/or progression of most cancer types and associated with nearly all aspects of the malignant phenotype of cancer, such as uncontrolled proliferation, resistance to cell death, invasiveness, angiogenesis and metastasis [1, 6]. Inhibition of PI3K/Akt signaling, therefore, may represent a promising anti-cancer strategy [6]. Thus, a better understanding of molecular mechanism in which the PI3K/Akt signaling pathway is dysregulated in various cancers might facilitate development of specific targeting therapies. Herein, we found that miR-93 was significantly upregulated in gliomas, and overexpressing miR-93 activated PI3K/Akt signaling through downregulating PTEN, PHLPP2 and FOXO3 expression via targeting their 3′UTRs, subsequently resulting in glioma cell proliferation and progression (Figure 7). Therefore, our results suggested that miR-93 contributes to progression of glioma and might represent as a potential therapeutic target for glioma therapy.


miR-93 promotes cell proliferation in gliomas through activation of PI3K/Akt signaling pathway.

Jiang L, Wang C, Lei F, Zhang L, Zhang X, Liu A, Wu G, Zhu J, Song L - Oncotarget (2015)

The model of miR-93-mediated PI3K/Akt signaling activation via down-regulation of PTEN, PHLPP2 and FOXO3 that results in the promotion of cell proliferation in gliomas
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480752&req=5

Figure 7: The model of miR-93-mediated PI3K/Akt signaling activation via down-regulation of PTEN, PHLPP2 and FOXO3 that results in the promotion of cell proliferation in gliomas
Mentions: Numerous studies have demonstrated that activation of the PI3K/Akt signaling pathway is essential to the development and/or progression of most cancer types and associated with nearly all aspects of the malignant phenotype of cancer, such as uncontrolled proliferation, resistance to cell death, invasiveness, angiogenesis and metastasis [1, 6]. Inhibition of PI3K/Akt signaling, therefore, may represent a promising anti-cancer strategy [6]. Thus, a better understanding of molecular mechanism in which the PI3K/Akt signaling pathway is dysregulated in various cancers might facilitate development of specific targeting therapies. Herein, we found that miR-93 was significantly upregulated in gliomas, and overexpressing miR-93 activated PI3K/Akt signaling through downregulating PTEN, PHLPP2 and FOXO3 expression via targeting their 3′UTRs, subsequently resulting in glioma cell proliferation and progression (Figure 7). Therefore, our results suggested that miR-93 contributes to progression of glioma and might represent as a potential therapeutic target for glioma therapy.

Bottom Line: Multiple regulators, such as phosphatase and tensin homolog (PTEN) and PH domain leucine rich repeat protein phosphatases (PHLPP), have also found to be involved in suppression of the PI3K/Akt signaling pathway.Furthermore, we found that overexpressing miR-93 promoted, but inhibition of miR-93 reduced, glioma cell proliferation and cell-cycle progression.Therefore, our results suggest that miR-93 might play an important role in glioma progression and uncover a novel mechanism for constitutive PI3K/Akt activation in gliomas.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, Guangzhou Medical University, Guangzhou 510182, China.

ABSTRACT
The PI3K/Akt signaling pathway is frequently activated in various human cancer types and plays essential roles in development and progression of cancers. Multiple regulators, such as phosphatase and tensin homolog (PTEN) and PH domain leucine rich repeat protein phosphatases (PHLPP), have also found to be involved in suppression of the PI3K/Akt signaling pathway. However, how suppressive effects mediated by these regulators are concomitantly disrupted in cancers, which display constitutively activated PI3K/Akt signaling, remains puzzling. In the present study, we reported that the expression of miR-93 was markedly upregulated in glioma cell lines and clinical glioma tissues. Statistical analysis revealed that miR-93 levels significantly correlated with clinicopathologic grade and overall survival in gliomas. Furthermore, we found that overexpressing miR-93 promoted, but inhibition of miR-93 reduced, glioma cell proliferation and cell-cycle progression. We demonstrated that miR-93 activated PI3K/Akt signaling through directly suppressing PTEN, PHLPP2 and FOXO3 expression via targeting their 3'UTRs. Therefore, our results suggest that miR-93 might play an important role in glioma progression and uncover a novel mechanism for constitutive PI3K/Akt activation in gliomas.

No MeSH data available.


Related in: MedlinePlus