Exploring miRNA-Associated Signatures with Diagnostic Relevance in Glioblastoma Multiforme and Breast  Cancer Patients

Leblanc, Véronique; Morin, Pier Jr

doi:10.3390/jcm4081612

Cited by 13 publications

(11 citation statements)

References 156 publications

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“…MicroRNAs can be either upregulated or downregulated, and function as oncogenes or tumor suppressors depending on their target genes (26). Accumulating evidence reveals the vital role of miRNAs involved in processes such as proliferation and invasion and in prognosis of GBM (27)(28)(29). It is well established that ZEB1 is a powerful regulator of EMT, and numerous miRNAs have been reported to be either direct or indirect regulators of EMT (30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR‑205 is associated with glioblastoma cell migration, invasion, and the epithelial-mesenchymal transition, by targeting ZEB1 via the Akt/mTOR signaling pathway

Chen

Kong

et al. 2017

Int J Oncol

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Glioblastoma (GBM) is the most common type of malignant brain tumor. In spite of recent advancements in surgical techniques, chemotherapy, and radiation therapy, patients with GBM often face a dire prognosis. MicroRNAs have been shown to modulate the aggressiveness of various cancers, and have emerged as possible therapeutic agents for the management of GBM. miR‑205 is dysregulated in glioma and act as a prognostic indicator. However, the role of miR‑205 in the development of GBM has not been elucidated. To better understand the pathogenesis of GBM, we examine the biological significance and molecular mechanisms of miR‑205 in GBM cells. Zinc finger E-box binding homeobox 1 (ZEB1) has been shown to regulate the epithelial-mesenchymal transition (EMT), which is strongly associated with GBM malignancy. In the present study, we show miR‑205 expression is reduced in GBM tissues and cell lines, and ZEB1 expression is inversely correlated with miR‑205 expression. We also show ZEB1 is a downstream target of miR‑205 and the Akt/mTOR signaling pathway is activated when miR‑205 interacts with ZEB1. Increased activity of miR‑205 in GBM cells significantly inhibits migration and invasion, and prevents EMT. Furthermore, overexpression of ZEB1 partially abolishes these inhibitory effects of miR‑205. We show that miR‑205 negatively regulates the expression of ZEB1 in GBM, inhibits cell migration and invasion, and prevents EMT, at least in part through the inhibition of the activation of the Akt/mTOR signaling pathway. Our results indicate miR‑205 may be an efficacious therapeutic agent in the treatment of GBM.

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Section: Discussionmentioning

confidence: 99%

Downregulation of miR‑205 is associated with glioblastoma cell migration, invasion, and the epithelial-mesenchymal transition, by targeting ZEB1 via the Akt/mTOR signaling pathway

Chen

Kong

et al. 2017

Int J Oncol

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“…[140] A growing body of evidence shows that miRNAs are one of the key players in cell differentiation and growth, mobility, and apoptosis. [141][142][143] Most microRNAs in animals are thought to function by inhibition of effective mRNA translation of target genes through imperfect base pairing with the 3-untranslated region of target mRNAs. [138,140] MiRNAs are appealing therapeutic targets and potential biomarkers of GBMs.…”

Section: Physically Facilitated Brain Drug-deliverymentioning

confidence: 99%

“…[138,140] MiRNAs are appealing therapeutic targets and potential biomarkers of GBMs. [141][142][143] Chan et al [144] were the first to investigate the functional properties of a single miRNA in GBM cell lines. They discovered that high expression of miR-21 is a common feature of GBM.…”

Section: Physically Facilitated Brain Drug-deliverymentioning

confidence: 99%

Tailored nanocarriers and bioconjugates for combating glioblastoma and other brain tumors

ElAmrawy¹,

Othman²,

Adkins³

et al. 2016

JCMT

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Worldwide, the incidence of primary brain tumors is on the rise. Unfortunately, noninvasive drug therapy is hampered by poor access of most drugs to the brain due to the insurmountable blood-brain barrier (BBB). Nanotechnology holds great promise for noninvasive therapy of severe brain diseases. Furthermore, recent bioconjugation strategies have enabled the invasion of the BBB via tailored-designed bioconjugates either with targeting moieties or alterations in the physicochemical and/or the pharmacokinetic parameters of central nervous system (CNS) active pharmaceutical ingredients. Multifunctional systems and new entities are being developed to target brain cells and tumor cells to resist the progression of brain tumors. Direct conjugation of an FDA-approved drug with a targeting moiety, diagnostic moiety, or pharmacokinetic-modifying moiety represents another current approach in combating brain tumors and metastases. Finally, genetic engineering, stem cells, and vaccinations are innovative nontraditional approaches described in different patents for the management of brain tumors and metastases. This review summarizes the recent technologies and patent applications in the past five years for the noninvasive treatment of glioblastoma and other brain tumors. Till now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are ongoing to bring novel CNS delivery systems to potential clinical application.

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“…For example, high levels of miR-21 occur in invasive breast tumors. There are two tumor suppressors among the miR-21 targets: tropomyosin I (TPMI) and phosphatase and tensin homolog (PTEN), plus the proteins involved in suppression, invasion, and metastasis: programed cell death 4 protein (PDCD4) and maspin ( 54 – 56 ).…”

Section: Micrornas In Aging and Breast Cancermentioning

confidence: 99%

Inflamma-miRs in Aging and Breast Cancer: Are They Reliable Players?

2015

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Human aging is characterized by chronic low-grade inflammation known as “inflammaging.” Persistent low-level inflammation also plays a key role in all stages of breast cancer since “inflammaging” is the potential link between cancer and aging through NF-kB pathways highly influenced by specific miRs. Micro-RNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at a posttranscriptional level. Inflamma-miRs have been implicated in the regulation of immune and inflammatory responses. Their abnormal expression contributes to the chronic pro-inflammatory status documented in normal aging and major age-related diseases (ARDs), inflammaging being a significant mortality risk factor in both cases. Nevertheless, the correct diagnosis of inflammaging is difficult to make and its hidden contribution to negative health outcomes remains unknown. This methodological work flow was aimed at defining crucial unanswered questions about inflammaging that can be used to clarify aging-related miRNAs in serum and cell lines as well as their targets, thus confirming their role in aging and breast cancer tumorigenesis. Moreover, we aim to highlight the links between the pro-inflammatory mechanism underlying the cancer and aging processes and the precise function of certain miRNAs in cellular senescence (CS). In addition, miRNAs and cancer genes represent the basis for new therapeutic findings indicating that both cancer and ARDs genes are possible candidates involved in CS and vice versa. Our goal is to obtain a focused review that could facilitate future approaches in the investigation of the mechanisms by which miRNAs control the aging process by acting as efficient ARDs inflammatory biomarkers. An understanding of the sources and modulation of inflamma-miRs along with the identification of their specific target genes could enhance their therapeutic potential.

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Exploring miRNA-Associated Signatures with Diagnostic Relevance in Glioblastoma Multiforme and Breast Cancer Patients

Cited by 13 publications

References 156 publications

Downregulation of miR‑205 is associated with glioblastoma cell migration, invasion, and the epithelial-mesenchymal transition, by targeting ZEB1 via the Akt/mTOR signaling pathway

Downregulation of miR‑205 is associated with glioblastoma cell migration, invasion, and the epithelial-mesenchymal transition, by targeting ZEB1 via the Akt/mTOR signaling pathway

Tailored nanocarriers and bioconjugates for combating glioblastoma and other brain tumors

Inflamma-miRs in Aging and Breast Cancer: Are They Reliable Players?

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