The Roles of miRNA in Glioblastoma Tumor Cell Communication: Diplomatic and Aggressive Negotiations

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(6), P. 1950 - 1950

Published: March 12, 2020

Glioblastoma (GBM) consists of a heterogeneous collection competing cellular clones which communicate with each other and the tumor microenvironment (TME). MicroRNAs (miRNAs) present various exchange mechanisms: free miRNA, extracellular vesicles (EVs), or gap junctions (GJs). GBM cells transfer miR-4519 miR-5096 to astrocytes through GJs. Oligodendrocytes located in invasion front high levels miR-219-5p, miR-219-2-3p, miR-338-3p, all related their differentiation. There is reciprocal between endothelial (ECs) as promotes angiogenesis after being transferred into ECs, whereas miR-145-5p acts suppressor. In glioma stem (GSCs), miR-1587 miR-3620-5p increase proliferation inhibits hormone receptor co-repressor-1 (NCOR1) EVs transfers. GBM-derived carry miR-21 miR-451 that are up-taken by microglia monocytes/macrophages, promoting proliferation. Macrophages release enriched cells. This bidirectional increases STAT3 activity macrophages, invasion, proliferation, angiogenesis, resistance treatment. miR-1238 upregulated resistant EVs, conferring adjacent via CAV1/EGFR signaling pathway. Decrypting these mechanisms could lead better patient stratification development novel target therapies.

Language: Английский

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Novel Function of lncRNA ADAMTS9-AS2 in Promoting Temozolomide Resistance in Glioblastoma via Upregulating the FUS/MDM2 Ubiquitination Axis

Frontiers in Cell and Developmental Biology, Journal Year: 2019, Volume and Issue: 7

Published: Oct. 2, 2019

Background: LncRNAs have been shown to play essential roles in cancer therapeutic response. However, the detailed mechanism of lncRNAs temozolomide (TMZ) resistance glioblastoma (GBM) remain be elucidated. Methods: To elucidate maintaining TMZ resistance, we constructed two TMZ-resistant GBM cell lines (T98G-R/U118-R). from four public datasets were reanalyzed, and candidate lncRNA ADAMTS9-AS2 was evaluated TMZ-treated patients vitro lines. Results: Reanalysis expression profiles identified as significantly overexpressed cells positively associated with IC50 cells. Overexpression also poor response shorter progression-free survival (PFS) patients. Knockdown inhibited proliferation attenuated TMZ, well mitigating invasion migration Subsequent investigations indicated that reduced suppressed FUS protein, which predicted a direct substrate ADAMTS9-AS2. Expression trends directly correlated those ADAMTS9-AS2, by increasing concentrations prolonged treatment TMZ. RNA pull-down RIP assays both endogenous exogenous binds RRM Znf_RanBP2 domains FUS, consequently protein expression. half-life decreased stability via K48 ubiquitin degradation. Moreover, E3 ubiquitin-protein ligase MDM2 interacts down regulates while facilitate its binding MDM2. interaction between mediates ubiquitination. Additionally, knockdown ADAMTS9-AS2/FUS signaling axis alleviated progression metastasis Conclusion: possessed novel function promotes upregulating FUS/MDM2 The or combination competitively inhibiting MDM2-dependent ubiquitination resulting enhanced resistance. Our results suggest ADAMTS9-AS2/ may represent suitable prognostic biomarker potential target therapy.

Language: Английский

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Roles of lncRNAs in cancer: Focusing on angiogenesis

Life Sciences, Journal Year: 2020, Volume and Issue: 252, P. 117647 - 117647

Published: April 8, 2020

Language: Английский

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Insights on the potential oncogenic impact of long non-coding RNA nicotinamide nucleotide transhydrogenase antisense RNA 1 in different cancer types; integrating pathway(s) and clinical outcome(s) association

Pathology - Research and Practice, Journal Year: 2022, Volume and Issue: 240, P. 154183 - 154183

Published: Oct. 20, 2022

Language: Английский

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Impact of epigenetic reprogramming on antitumor immune responses in glioma

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(2)

Published: Jan. 16, 2023

Epigenetic remodeling is a molecular hallmark of gliomas, and it has been identified as key mediator glioma progression. dysregulation contributes to gliomagenesis, tumor progression, responses immunotherapies, well determining clinical features. This epigenetic includes changes in histone modifications, chromatin structure, DNA methylation, all which are driven by mutations genes such 3 (H3C1 H3F3A), isocitrate dehydrogenase 1/2 (IDH1/2), α-thalassemia/mental retardation, X-linked (ATRX), additional remodelers. Although much the initial research primarily how aberrations impacted progression solely examining cells, recent studies have aimed at establishing role alterations shaping microenvironment (TME). In this review, we discuss mechanisms these phenomena remodel TME current therapies targeting affect immune response therapeutic outcomes. Understanding link between provides insights into implementation epigenetic-targeting improve antitumor response.

Language: Английский

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A TGF‐β signaling‐related lncRNA signature for prediction of glioma prognosis, immune microenvironment, and immunotherapy response

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 30(4)

Published: Oct. 18, 2023

Abstract Aims The dysregulation of TGF‐β signaling is a crucial pathophysiological process in tumorigenesis and progression. LncRNAs have diverse biological functions are significant participants the regulation tumor pathways. However, clinical value lncRNAs related to glioma currently unclear. Methods Data on glioma's RNA‐seq transcriptome, somatic mutation, DNA methylation data, clinicopathological information were derived from CGGA TCGA databases. A prognostic lncRNA signature was constructed by Cox LASSO regression analyses. TIMER2.0 database utilized deduce immune infiltration characteristics. “ELMER v.2” used reconstruct TF‐methylation‐gene regulatory network. Immunotherapy chemotherapy response predictions implemented TIDE algorithm GDSC database, respectively. In vitro vivo experiments conducted verify results clarify mechanism lncRNA. Results glioma, signaling‐related 15‐lncRNA constructed, including AC010173.1, HOXA‐AS2, AC074286.1, AL592424.1, DRAIC, HOXC13‐AS, AC007938.1, AC010729.1, AC013472.3, AC093895.1, AC131097.4, AL606970.4, HOXC‐AS1, AGAP2‐AS1, AC002456.1. This proved be reliable tool, with high risk indicating an unfavorable prognosis being linked malignant genomic mutation traits. Risk levels associated different landscapes, where indicative macrophage infiltration. addition, also suggested better immunotherapy response. cg05987823 important site progression, AP‐1 transcription factor family participated expression. AGAP2‐AS1 knockdown inhibited proliferation, migration, invasion cells, as well growth downregulating expression NF‐κB ERK 1/2 pathway. Conclusions established which can for judgment, status inference, prediction. plays role

Language: Английский

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Roles of STAT3 in the pathogenesis and treatment of glioblastoma

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Feb. 27, 2023

Glioblastoma (GBM) is the most malignant of astrocytomas mainly involving cerebral hemispheres and cortex. It one fatal refractory solid tumors, with a 5-year survival rate merely 5% among adults. IL6/JAK/STAT3 an important signaling pathway involved in pathogenesis progression GBM. The expression STAT3 GBM tissues substantially higher than that normal brain cells. abnormal activation renders tumor microenvironment immunosuppression. Besides, blocking can effectively inhibit growth metastasis On this basis, inhibition may be new therapeutic approach for GBM, combination targeted therapy conventional therapies improve current status treatment. This review summarized roles feasibility target therapy.

Language: Английский

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Extracellular vesicles released by glioma cells are decorated by Annexin A2 allowing for cellular uptake via heparan sulfate

Cancer Gene Therapy, Journal Year: 2023, Volume and Issue: 30(8), P. 1156 - 1166

Published: May 25, 2023

Language: Английский

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Role of LGMN in tumor development and its progression and connection with the tumor microenvironment

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Feb. 7, 2023

Legumain (LGMN) has been demonstrated to be overexpressed not just in breast, prostatic, and liver tumor cells, but also the macrophages that compose microenvironment. This supports idea LGMN is a pivotal protein regulating development, invasion, dissemination. Targeting with siRNA or chemotherapeutic medicines peptides can suppress cancer cell proliferation culture reduce growth vivo. Furthermore, legumain used as marker for detection targeting due its expression being significantly lower normal cells compared tumors tumor-associated (TAMs). Tumor formation influenced by aberrant of proteins alterations cellular architecture, microenvironment crucial deciding factor. an vivo-active cysteine protease catalyzes degradation numerous proteins. Its precise biological mechanism encompasses number routes, including effects on macrophage neovascular endothelium The purpose this work establish rationale thoroughly investigating function discovering novel early diagnosis markers therapeutic targets reviewing genesis progression relationship milieu.

Language: Английский

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Exosomes in Glioma: Unraveling Their Roles in Progression, Diagnosis, and Therapy

Cancers, Journal Year: 2024, Volume and Issue: 16(4), P. 823 - 823

Published: Feb. 18, 2024

Gliomas, the most prevalent primary malignant brain tumors, present a challenging prognosis even after undergoing surgery, radiation, and chemotherapy. Exosomes, nano-sized extracellular vesicles secreted by various cells, play pivotal role in glioma progression contribute to resistance against chemotherapy radiotherapy facilitating transportation of biological molecules promoting intercellular communication within tumor microenvironment. Moreover, exosomes exhibit remarkable ability traverse blood–brain barrier, positioning them as potent carriers for therapeutic delivery. These attributes hold promise enhancing diagnosis, prognosis, treatment. Recent years have witnessed significant advancements exosome research realm tumors. In this article, we primarily focus on elucidating development, highlighting latest breakthroughs diagnostic approaches, outlining prospective directions future research.

Language: Английский

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