Increased expression of microRNA-9 predicts an unfavorable prognosis in human glioma

Wu, Zhenyu; Wang, Liang; Li, Gang; Liu, Hui; Fan, Feiyan; Li, Zhaobo; Li, Yunqing; Gao, Guodong

doi:10.1007/s11010-013-1805-5

Cited by 39 publications

(30 citation statements)

References 23 publications

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“…These findings appeared in agreement with a previous study by Tan et al, who reported that a balance between cyclic AMP response element-binding protein (CREB) and miR-9 determines the proliferation or migration status of glioma cells, whereby miR-9 promotes migration and CREB induces proliferation [13]. Moreover, as miR-9 expression is an independent prognostic factor for overall survival in glioma patients [14], we elected to further investigate this miRNA.…”

Section: Resultssupporting

confidence: 90%

Density-Dependent Regulation of Glioma Cell Proliferation and Invasion Mediated by miR-9

Katakowski

Charteris

Chopp

et al. 2016

Cancer Microenvironment

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The phenotypic axis of invasion and proliferation in malignant glioma cells is a well-documented phenomenon. Invasive glioma cells exhibit a decreased proliferation rate and a resistance to apoptosis, and invasive tumor cells dispersed in brain subsequently revert to proliferation and contribute to secondary tumor formation. One miRNA can affect dozens of mRNAs, and some miRNAs are potent oncogenes. Multiple miRNAs are implicated in glioma malignancy, and several of which have been identified to regulate tumor cell motility and division. Using rat 9 L gliosarcoma and human U87 glioblastoma cell lines, we investigated miRNAs associated with the switch between glioma cell invasion and proliferation. Using micro-dissection of 9 L glioma tumor xenografts in rat brain, we identified disparate expression of miR-9 between cells within the periphery of the primary tumor, and those comprising tumor islets within the invasive zone. Modifying miR-9 expression in in vitro assays, we report that miR-9 controls the axis of glioma cell invasion/proliferation, and that its contribution to invasion or proliferation is biphasic and dependent upon local tumor cell density. In addition, immunohistochemistry revealed elevated hypoxia inducible factor 1 alpha (HIF-1α) in the invasive zone as compared to the primary tumor periphery. We also found that hypoxia promotes miR-9 expression in glioma cells. Based upon these findings, we propose a hypothesis for the contribution of miR-9 to the dynamics glioma invasion and satellite tumor formation in brain adjacent to tumor.

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Section: Resultssupporting

confidence: 90%

Density-Dependent Regulation of Glioma Cell Proliferation and Invasion Mediated by miR-9

Katakowski

Charteris

Chopp

et al. 2016

Cancer Microenvironment

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“…46 More complicated, its increased expression was shown to be a favorable prognostic factor in medulloblastoma in one report, 47 but a poor prognostic factor in glioma in another study. 48 For AML, miR-9 is the most specifically up-regulated microRNA in MLL-rearranged AML compared with other types of AML, as it is a target of MLL fusion proteins, and its expression directly correlates with disease progression. 49 In our study, miR-9 was an unfavorable prognostic factor.…”

Section: Discussionmentioning

confidence: 99%

A 3-microRNA scoring system for prognostication in de novo acute myeloid leukemia patients

Chou

et al. 2014

Leukemia

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As a highly heterogeneous disease, acute myeloid leukemia (AML) needs fine risk stratification to get an optimal outcome of patients. MicroRNAs have florid biological functions and have critical roles in the pathogenesis and prognosis in AML. Expression levels of some single microRNAs are influential for prognosis, but a system integrating several together and considering the weight of each should be more powerful. We thus analyzed the clinical, genetic and microRNA profiling data of 138 de novo AML patients of our institute. By multivariate analysis, we identified that high expression of hsa-miR-9-5p and hsa-miR-155-5p were independent poor prognostic factors, whereas that of hsa-miR-203 had a trend to be a favorable factor. We constructed a scoring system from expression of these three microRNAs by considering the weight of each. The scores correlated with distinct clinical and biological features and outperformed single microRNA expression in prognostication. In both ours and another validation cohort, higher scores were associated with shorter overall survival, independent of other well-known prognostic factors. By analyzing the mRNA expression profiles, we sorted out several cancer-related pathways highly correlated with the microRNA prognostic signature. We conclude that this 3-microRNA scoring system is simple and powerful for risk stratification of de novo AML patients.

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“…Among the regulatory roles of miRs is the coordination of development and the parallel process, oncogenesis. MiR-9 is known to have critical roles in neuron development and migration [30] , yet has been associated with malignancies of the CNS such as GBM and Medulloblastoma [31,32] . MiR-9 also has important roles in the development of cancers outside of the CNS such as breast, colon, cervical, ovarian, and gastric cancer [33–36] .…”

Section: Discussionmentioning

confidence: 99%

Temozolomide resistance and tumor recurrence: Halting the Hedgehog

Munoz

Rodriguez-Cruz

Walker

et al. 2015

Can Cell Microenviron

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Chemotherapy with Temozolomide (TMZ), radiation and surgery are the primary methods to treat Glioblastoma Multiforme (GBM), the most common adult intracranial tumor with dismal outcome. GBM resistance to therapy is the main reason of poor patient outcomes. Thus, methods to overcome the resistance are an area of extensive research. This highlight focuses on three recently published articles on the mechanism of resistance and possible therapeutic intervention, including RNA treatment with stem cells. We showed a crucial role of the developmental Sonic Hedgehog (SHH) pathway in the acquisition and maintenance of TMZ resistance. SHH signaling caused TMZ resistance in GBM cells through an increase in the multiple drug resistance gene (MDR1). The SHH receptor, Patched-1 (PTCH1), negatively regulate SHH signaling. In GBM, miR-9 suppressed PTCH1 levels, resulting in the activation of SHH pathway. Thus, SHH signaling is independent of the ligand in resistant GBM cells. MiR-9 was also increased in chemoresistance CD133+ GBM cells. A potential method to reverse resistance was tested by delivering the anti-miR in bone marrow-derived Mesenchymal Stem Cells (MSCs). The anti-miR-9 was transferred into the resistant GBM cells through exosomes and gap junctional intercellular communication. We also review on-going clinical trials with inhibitor of SHH signaling, and also discuss drug delivery by cell therapy for GBM. While GBM treatment has proven to be a challenge, there are a number of novel approaches we are currently developing to manage this malignancy.

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Increased expression of microRNA-9 predicts an unfavorable prognosis in human glioma

Cited by 39 publications

References 23 publications

Density-Dependent Regulation of Glioma Cell Proliferation and Invasion Mediated by miR-9

Density-Dependent Regulation of Glioma Cell Proliferation and Invasion Mediated by miR-9

A 3-microRNA scoring system for prognostication in de novo acute myeloid leukemia patients

Temozolomide resistance and tumor recurrence: Halting the Hedgehog

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