Epigenetic silencing of miR-338 facilitates glioblastoma progression by de-repressing the pyruvate kinase M2-β-catenin axis

Han, Bo; Meng, Xiangqi; Chen, Hui; Chen, Lingchao; Liu, Xing; Wang, Hongjun; Liu, Daming; Gao, Fei; Lin, Lin; Ming, Jianguang; Sun, Bo; Yin, Shi; Wang, Ruijia; Wu, Pengfei; Jiang, Chuanlu

doi:10.18632/aging.101271

Cited by 17 publications

(16 citation statements)

References 38 publications

(32 reference statements)

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“…38,39 Dysregulation of miRNA was pivotal for the development of glioma. 40 Previous studies have found that PTEN could be targeted by several miRNAs including miR-130a, miR-374b and miR-190a-3p. 25,41,42 We found that miR-190a-3p targeted PTEN in glioma cells which was consistent with a recent report.…”

Section: Discussionmentioning

confidence: 99%

<p>Long Non-Coding RNA PART1 Exerts Tumor Suppressive Functions in Glioma via Sponging miR-190a-3p and Inactivation of PTEN/AKT Pathway</p>

Jin

Piao

Sun

et al. 2020

OTT

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Background: Glioma is the most commonly diagnosed primary brain tumor. Dysregulation of long non-coding RNA (lncRNA) is associated with initiation and development of various cancer types including glioma. Methods: The relative expression of lncRNA was analyzed by real time-quantitative polymerase chain reaction (RT-qPCR). Cell counting kit (CCK-8) and flow cytometry analysis were applied to explore the role of prostate androgen-regulated transcript 1 (PART1) in glioma cell lines. Luciferase reporter assay, Western blotting and RT-qPCR were used to investigate the association between PART1, miR-190a-3p and phosphatase and tensin homolog deleted on chromosome ten (PTEN) in glioma cell lines. Results: In the present study, we elucidated a pivotal role and molecular mechanism of lncRNA PART1 in glioma cell lines. It was found that PART1 was significantly downregulated in glioma tissues compared to normal tissues according to TCGA data and our RT-qPCR results. The cell-based assays showed that PART1 suppressed cell proliferation and triggered cell apoptosis in glioma cell lines. PART1 inactivated PI3K/AKT cascade in glioma cell lines. Transfection of constitutively activated AKT (Myr-AKT) reversed PART1 induced cell apoptosis and cell growth arrest. The bioinformatic analysis suggested that miR-190a-3p might bind to PART1. In the dual luciferase reporter assay, we validated that PART1 directly bound to miR-190a-3p in glioma cell lines. Furthermore, there was a reciprocal repression between PART1 and miR-190-3p. In addition, PART1 upregulated PTEN and inactivated PI3K/AKT pathway in glioma cell lines. Moreover, silencing of PTEN reversed PART1 overexpression induced cell growth arrest and apoptosis. In glioma tissues, the Pearson Correlation analysis showed that there was a strong-positive correlation between PART1 level and PTEN mRNA level. Conclusion: Taken together, the current study revealed a PART1/miR-190a-3p/PTEN/PI3K/ AKT axis in glioma and provided novel insights for understanding the complex lncRNA-miRNA network in glioma.

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Section: Discussionmentioning

confidence: 99%

<p>Long Non-Coding RNA PART1 Exerts Tumor Suppressive Functions in Glioma via Sponging miR-190a-3p and Inactivation of PTEN/AKT Pathway</p>

Jin

Piao

Sun

et al. 2020

OTT

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“…TMZ is demonstrated as the first-line chemotherapy drug in patients with glioma 41 . However, the survival rates still remain low from inherent TMZ resistance or relapse with chemotherapyresistant gliomas 42,43 . Currently, there are few alternate treatment options for patients with TMZ-resistant gliomas, and adjuvant TMZ chemotherapy options are a popular area of intense research 33 .…”

Section: Discussionmentioning

confidence: 99%

Dual functionalized brain-targeting nanoinhibitors restrain temozolomide-resistant glioma via attenuating EGFR and MET signaling pathways

et al. 2020

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Activation of receptor tyrosine kinase (RTK) protein is frequently observed in malignant progression of gliomas. In this study, the crosstalk activation of epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) signaling pathways is demonstrated to contribute to temozolomide (TMZ) resistance, resulting in an unfavorable prognosis for patients with glioblastoma. To simultaneously mitigate EGFR and MET activation, a dual functionalized brain-targeting nanoinhibitor, BIP-MPC-NP, is developed by conjugating Inherbin3 and cMBP on the surface of NHS-PEG 8-Mal modified MPCnanoparticles. In the presence of BIP-MPC-NP, DNA damage repair is attenuated and TMZ sensitivity is enhanced via the down-regulation of E2F1 mediated by TTP in TMZ resistant glioma. In vivo magnetic resonance imaging (MRI) shows a significant repression in tumor growth and a prolonged survival of mice after injection of the BIP-MPC-NP and TMZ. These results demonstrate the promise of this nanoinhibitor as a feasible strategy overcoming TMZ resistance in glioma.

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“…Interestingly, the knockdown of this miRNA by the injection of the miRNA-338-sponge in mice brain promoted spontaneous neoplasm formation, histologically reminiscent of GBM with neuronal morphological disorganization and increased proliferation ( Howe et al, 2017 ). This data is of utmost importance as miRNA-338 is severely downregulated in GBM ( Han et al, 2017 ), and the solely fact that its downregulation promotes neoplasm formation indicates that it is a key player for developing brain tumors. Besides, miRNA-338 is highly expressed in mature neurons, and its overexpression in GBM cell lines decreased their proliferation ( Howe et al, 2017 ).…”

Section: Mirnas As Modulators Of Parkinson’s and Alzheimer’s Diseasesmentioning

confidence: 97%

“…miRNA-338 regulates migration, invasion, proliferation, and apoptosis of tumor cells and was found to be downregulated in GBM possibly due to hypermethylation of its promoter ( Han et al, 2017 ). Recently, the EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1), which controls MMPs, and the metalloproteinase inhibitor (TIMP)-3 were identified as targets of miRNA-338 ( Klenotic et al, 2004 ; Lei et al, 2017 ).…”

Section: Evs – Mirnas In the Regulation Of Gbmmentioning

confidence: 99%

“…However, miRNA-338 was also found to be upregulated in GBM, when compared to lower grades gliomas, and to promote tumor invasiveness by increasing the expression of MMP2 by downregulating t-shirt zinc finger homeobox (TSHZ) 3, a transcription factor involved in development ( Li et al, 2018 ). Furthermore, miRNA-338 targets embryonic pyruvate kinase M2 (PKM2), frequently overexpressed in tumors, preventing the transcriptional activity of β-catenin and leading to decreased tumor growth and increased survival of the animal model ( Han et al, 2017 ). Moreover, it was discovered that miRNA-338 is regulated by LINC00689, a long non-coding RNA, whose expression is incremented in glioma tissue where it promotes glycolysis, migration, proliferation, and invasion ( Liu X. et al, 2019 ).…”

Section: Evs – Mirnas In the Regulation Of Gbmmentioning

confidence: 99%

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Extracellular Vesicles Loaded miRNAs as Potential Modulators Shared Between Glioblastoma, and Parkinson’s and Alzheimer’s Diseases

Thomas

Florio

Perez-Castro

2020

Front. Cell. Neurosci.

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Glioblastoma (GBM) is the deadliest brain tumor. Its poor prognosis is due to cell heterogeneity, invasiveness, and high vascularization that impede an efficient therapeutic approach. In the past few years, several molecular links connecting GBM to neurodegenerative diseases (NDDs) were identified at preclinical and clinical level. In particular, giving the increasing critical role that epigenetic alterations play in both GBM and NDDs, we deeply analyzed the role of miRNAs, small non-coding RNAs acting epigenetic modulators in several key biological processes. Specific miRNAs, transported by extracellular vesicles (EVs), act as intercellular communication signals in both diseases. In this way, miRNA-loaded EVs modulate GBM tumorigenesis, as they spread oncogenic signaling within brain parenchyma, and control the aggregation of neurotoxic protein (Tau, Aβ-amyloid peptide, and α-synuclein) in NDDs. In this review, we highlight the most promising miRNAs linking GBM and NDDs playing a significant pathogenic role in both diseases.

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Epigenetic silencing of miR-338 facilitates glioblastoma progression by de-repressing the pyruvate kinase M2-β-catenin axis

Cited by 17 publications

References 38 publications

<p>Long Non-Coding RNA PART1 Exerts Tumor Suppressive Functions in Glioma via Sponging miR-190a-3p and Inactivation of PTEN/AKT Pathway</p>

<p>Long Non-Coding RNA PART1 Exerts Tumor Suppressive Functions in Glioma via Sponging miR-190a-3p and Inactivation of PTEN/AKT Pathway</p>

Dual functionalized brain-targeting nanoinhibitors restrain temozolomide-resistant glioma via attenuating EGFR and MET signaling pathways

Extracellular Vesicles Loaded miRNAs as Potential Modulators Shared Between Glioblastoma, and Parkinson’s and Alzheimer’s Diseases

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