Oligonucleotide Therapeutics as a New Class of Drugs for Malignant Brain Tumors: Targeting mRNAs, Regulatory RNAs, Mutations, Combinations, and Beyond

Krichevsky, Anna M.; Uhlmann, Erik J.

doi:10.1007/s13311-018-00702-3

Cited by 37 publications

(39 citation statements)

References 384 publications

(361 reference statements)

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“…The evidences on critical role of miRNAs in the formation and progression of glioma enable some of them to emerge as clinical markers in diagnosis, prognosis, as well as novel agents in mitigation of GBM. Recently, advancements on oligonucleotides delivery (selective targeting with Aptamers, Cell-Penetrating Peptides, and Nanoparticles) to the brain and malignant gliomas via local and systemic have been achieved [66]. Particularly, different types of nanoparticles [67], have been rationalized for optimal benefit in different pathological states including neuronal cancers.…”

Section: Discussionmentioning

confidence: 99%

Mir-370-3p Impairs Glioblastoma Stem-Like Cell Malignancy Regulating a Complex Interplay between HMGA2/HIF1A and the Oncogenic Long Non-Coding RNA (lncRNA) NEAT1

Lulli

Buccarelli

Ilari

et al. 2020

IJMS

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Glioblastoma (GBM) is the most aggressive and prevalent form of a human brain tumor in adults. Several data have demonstrated the implication of microRNAs (miRNAs) in tumorigenicity of GBM stem-like cells (GSCs). The regulatory functions of miRNAs in GSCs have emerged as potential therapeutic candidates for glioma treatment. The current study aimed at investigating the function of miR-370-3p in glioma progression, as aberrant expression of miR-370-3p, is involved in various human cancers, including glioma. Analyzing our collection of GBM samples and patient-derived GSC lines, we found the expression of miR-370-3p significantly downregulated compared to normal brain tissues and normal neural stem cells. Restoration of miR-370-3p expression in GSCs significantly decreased proliferation, migration, and clonogenic abilities of GSCs, in vitro, and tumor growth in vivo. Gene expression analysis performed on miR-370-3p transduced GSCs, identified several transcripts involved in Epithelial to Mesenchymal Transition (EMT), and Hypoxia signaling pathways. Among the genes downregulated by the restored expression of miR-370-3p, we found the EMT-inducer high-mobility group AT-hook 2 (HMGA2), the master transcriptional regulator of the adaptive response to hypoxia, Hypoxia-inducible factor (HIF)1A, and the long non-coding RNAs (lncRNAs) Nuclear Enriched Abundant Transcript (NEAT)1. NEAT1 acts as an oncogene in a series of human cancers including gliomas, where it is regulated by the Epidermal Growth Factor Receptor (EGFR) pathways, and contributes to tumor growth and invasion. Noteworthy, the expression levels of miR-370-3p and NEAT1 were inversely related in both GBM tumor specimens and GSCs, and a dual-luciferase reporter assay proved the direct binding between miR-370-3p and the lncRNAs NEAT1. Our results identify a critical role of miR-370-3p in the regulation of GBM development, indicating that miR-370-3p acts as a tumor-suppressor factor inhibiting glioma cell growth, migration and invasion by targeting the lncRNAs NEAT1, HMGA2, and HIF1A, thus, providing a potential candidate for GBM patient treatment.

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Section: Discussionmentioning

confidence: 99%

Mir-370-3p Impairs Glioblastoma Stem-Like Cell Malignancy Regulating a Complex Interplay between HMGA2/HIF1A and the Oncogenic Long Non-Coding RNA (lncRNA) NEAT1

Lulli

Buccarelli

Ilari

et al. 2020

IJMS

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“…To identify candidate miRNAs of increased therapeutic importance, both upregulated and downregulated miRNAs in primary and metastatic brain cancers were compared. Based on the existing literature, differentially expressed miRNAs in GBM [117][118][119][120][121][122][123][124][125][126][127][128][129] and BrM [130][131][132][133][134][135][136][137] were grouped, which resulted in four different groups, including GBM upregulated, GBM downregulated, BrM upregulated, and BrM downregulated. Venn diagram-based comparison of miRNAs was then performed to identify the putative miRNAs of therapeutic importance ( Figure 2 and Table 1), and differentially expressed miRNAs in both GBM and BrM are discussed in detail below.…”

Section: Mirnas Differentially Regulated In Brain Cancermentioning

confidence: 99%

Therapeutically Significant MicroRNAs in Primary and Metastatic Brain Malignancies

Akilandeswari

Larcher

Chen

et al. 2020

Cancers

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Brain cancer is one among the rare cancers with high mortality rate that affects both children and adults. The most aggressive form of primary brain tumor is glioblastoma. Secondary brain tumors most commonly metastasize from primary cancers of lung, breast, or melanoma. The five-year survival of primary and secondary brain tumors is 34% and 2.4%, respectively. Owing to poor prognosis, tumor heterogeneity, increased tumor relapse, and resistance to therapies, brain cancers have high mortality and poor survival rates compared to other cancers. Early diagnosis, effective targeted treatments, and improved prognosis have the potential to increase the survival rate of patients with primary and secondary brain malignancies. MicroRNAs (miRNAs) are short noncoding RNAs of approximately 18–22 nucleotides that play a significant role in the regulation of multiple genes. With growing interest in the development of miRNA-based therapeutics, it is crucial to understand the differential role of these miRNAs in the given cancer scenario. This review focuses on the differential expression of ten miRNAs (miR-145, miR-31, miR-451, miR-19a, miR-143, miR-125b, miR-328, miR-210, miR-146a, and miR-126) in glioblastoma and brain metastasis. These miRNAs are highly dysregulated in both primary and metastatic brain tumors, which necessitates a better understanding of their role in these cancers. In the context of the tumor microenvironment and the expression of different genes, these miRNAs possess both oncogenic and/or tumor-suppressive roles within the same cancer.

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“…Scheme outlining the differences between DNA (left) and PNA (right) monomers be insulin-like growth factors, fibroblast growth factor and their receptors [74,75] . Excellent review articles describing current therapeutic approaches and novel trends in GBM management are available [69,[76][77][78][79][80][81][82] .…”

Section: Glioblastomamentioning

confidence: 99%

Peptide nucleic acid-based targeting of microRNAs: possible therapeutic applications for glioblastoma

Gambari¹,

Gasparello²,

Finotti³

2019

JCMT

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A large and incremental number of non-coding RNAs, including microRNAs (miRNAs) have been recently demonstrated to play a very important role in human pathologies, including cancer. Therefore, microRNAs have been proposed as therapeutic targets and molecules exhibiting anti-miRNA activity or mimicking functional miRNAs have been developed. Among biomolecules proposed in anti-miRNA therapy, peptide nucleic acids (PNAs) are appealing, in consideration of their stability and efficacy in recognizing RNA targets. PNAs against tumor associated miRNAs have proven to be efficient in inducing anti-tumor effects both in vitro and in vivo. For instance, PNAs targeting miR-155-5p are able to induce apoptosis in glioma cell lines and to enhance the sensitivity to temozolomide (TMZ) in TMZ resistant glioma cells. In vivo, PNAs anti-miR-21 were found to exhibit anti-tumor effects associated with improved survival when administered to animals with intracranial gliomas.

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Oligonucleotide Therapeutics as a New Class of Drugs for Malignant Brain Tumors: Targeting mRNAs, Regulatory RNAs, Mutations, Combinations, and Beyond

Cited by 37 publications

References 384 publications

Mir-370-3p Impairs Glioblastoma Stem-Like Cell Malignancy Regulating a Complex Interplay between HMGA2/HIF1A and the Oncogenic Long Non-Coding RNA (lncRNA) NEAT1

Mir-370-3p Impairs Glioblastoma Stem-Like Cell Malignancy Regulating a Complex Interplay between HMGA2/HIF1A and the Oncogenic Long Non-Coding RNA (lncRNA) NEAT1

Therapeutically Significant MicroRNAs in Primary and Metastatic Brain Malignancies

Peptide nucleic acid-based targeting of microRNAs: possible therapeutic applications for glioblastoma

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