Targeting Long Non-coding RNA to Therapeutically Regulate Gene Expression in Cancer DOI Creative Commons
Da Fu, Yi Shi, Ji‐Bin Liu

et al.

Molecular Therapy — Nucleic Acids, Journal Year: 2020, Volume and Issue: 21, P. 712 - 724

Published: July 10, 2020

Long-chain non-coding RNAs (lncRNAs) are RNA molecules with a length greater than 200 nt and no function of encoding proteins. lncRNAs play precise regulatory at different levels transcription post-transcription, they interact various factors to regulate gene expression, then participate in cell growth, differentiation, apoptosis, other life processes. In recent years, studies have shown that the abnormal expression is closely related occurrence development tumors, which expected become an effective biomarker tumor diagnosis. The sequencing analysis mutations whole genome suggests regions may important role tumors. Therefore, in-depth study helpful clarify molecular mechanism provide new targets for diagnosis treatment. This review introduces clinical application prospect affecting from perspective regulation.

Language: Английский

LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer DOI Creative Commons
Yun Wang,

Jia-Huan Lu,

Qi-Nian Wu

et al.

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: Dec. 1, 2019

Abstract Background Long noncoding RNAs (lncRNAs) play nonnegligible roles in the epigenetic regulation of cancer cells. This study aimed to identify a specific lncRNA that promotes colorectal (CRC) progression and could be potential therapeutic target. Methods We screened highly expressed lncRNAs human CRC samples compared with their matched adjacent normal tissues. The proteins interact LINRIS (Long Intergenic Noncoding RNA for IGF2BP2 Stability) were confirmed by pull-down immunoprecipitation (RIP) assays. proliferation metabolic alteration cells inhibited tested vitro vivo . Results was upregulated tissues from patients poor overall survival (OS), inhibition led impaired cell line growth. Moreover, knockdown resulted decreased level insulin-like growth factor 2 mRNA-binding protein (IGF2BP2), newly found N 6 -methyladenosine (m A) ‘reader’. blocked K139 ubiquitination IGF2BP2, maintaining its stability. process prevented degradation through autophagy-lysosome pathway (ALP). Therefore, attenuated downstream effects especially MYC-mediated glycolysis In addition, transcription GATA3 experiments showed suppressed tumors orthotopic models patient-derived xenograft (PDX) models. Conclusion is an independent prognostic biomarker CRC. -IGF2BP2-MYC axis promising

Language: Английский

Citations

417
Exosomal noncoding RNAs in Glioma: biological functions and potential clinical applications DOI Creative Commons
Jian Cheng,

Jinli Meng,

Lei Zhu

et al.

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: March 25, 2020

Abstract Gliomas are complex and heterogeneous brain tumors with poor prognosis. Glioma cells can communicate their surroundings to create a tumor-permissive microenvironment. Exosomes represent new means of intercellular communication by delivering various bioactive molecules, including proteins, lipids nucleic acids, participate in tumor initiation progression. Noncoding RNAs (ncRNAs) microRNA, long-noncoding RNA, circular account for large portion human transcriptome play important roles pathophysiological processes, especially cancers. In addition, ncRNAs be selectively packaged, secreted transferred between exosomes modulate numerous hallmarks glioma, such as proliferation, invasion, angiogenesis, immune-escape, treatment resistance. Hence, the strategies specifically targeting exosomal could attractive therapeutic options. able cross blood barrier (BBB), readily accessible nearly all types biofluids, which make them promising biomarkers gliomas. Additionally, given biocompatibility exosomes, they engineered deliver factors, proteins drugs, target applications. Here, we reviewed current research on glioma We also discussed potential clinical applications novel therapeutics.

Language: Английский

Citations

268
Prognostic and Predictive Biomarkers in Gliomas DOI Open Access
Paulina Śledzińska, Marek Bebyn, Jacek Furtak

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(19), P. 10373 - 10373

Published: Sept. 26, 2021

Gliomas are the most common central nervous system tumors. New technologies, including genetic research and advanced statistical methods, revolutionize therapeutic approach to patient reveal new points of treatment options. Moreover, 2021 World Health Organization Classification Tumors Central Nervous System has fundamentally changed classification gliomas incorporated many molecular biomarkers. Given rapid progress in neuro-oncology, here we compile latest on prognostic predictive biomarkers gliomas. In adult patients, IDH mutations positive markers have greatest significance. However, CDKN2A deletion, IDH-mutant astrocytomas, is a marker highest malignancy grade. presence TERT promoter mutations, EGFR alterations, or combination chromosome 7 gain 10 loss upgrade IDH-wildtype astrocytoma glioblastoma. pediatric H3F3A alterations important which predict worse outcome. MGMT methylation clinical significance predicting responses temozolomide (TMZ). Conversely, mismatch repair defects cause hypermutation phenotype poor response TMZ. Finally, discussed liquid biopsies, promising diagnostic, prognostic, techniques, but further work needed implement these novel technologies practice.

Language: Английский

Citations

251
The RING finger protein family in health and disease DOI Creative Commons
Chunmei Cai, Yan‐Dong Tang, Jingbo Zhai

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Aug. 30, 2022

Ubiquitination is a highly conserved and fundamental posttranslational modification (PTM) in all eukaryotes regulating thousands of proteins. The RING (really interesting new gene) finger (RNF) protein, containing the domain, exerts E3 ubiquitin ligase that mediates covalent attachment (Ub) to target Multiple reviews have summarized critical roles tripartite-motif (TRIM) protein family, subgroup RNF proteins, various diseases, including cancer, inflammatory, infectious, neuropsychiatric disorders. Except for TRIMs, since numerous studies over past decades delineated other proteins also exert widespread involvement several their importance should not be underestimated. This review summarizes potential contribution dysregulated except pathogenesis some autoimmune neurodegenerative disorder. Since viral infection broadly involved induction development those this manuscript highlights regulatory excluding antiviral immune responses. In addition, we further discuss intervention strategies targeting prevention therapeutics human diseases.

Language: Английский

Citations

107
Glioblastoma Therapy: Past, Present and Future DOI Open Access
Elena Obrador, Paz Moreno-Murciano, María Oriol‐Caballo

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2529 - 2529

Published: Feb. 21, 2024

Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians researchers, no significant improvement in survival has achieved since Stupp protocol became standard care (SOC) 2005. Despite multimodality treatments, recurrence is almost universal with rates under 2 years after diagnosis. Here, we discuss recent progress our understanding GB pathophysiology, particular, importance glioma stem cells (GSCs), tumor microenvironment conditions, epigenetic mechanisms involved growth, aggressiveness recurrence. The discussion on therapeutic strategies first covers SOC treatment targeted therapies that shown to interfere different signaling pathways (pRB/CDK4/RB1/P16

Language: Английский

Citations

64
Exploring ncRNA-mediated regulation of EGFR signalling in glioblastoma: From mechanisms to therapeutics DOI
Riya Thapa, Muhammad Afzal, Ahsas Goyal

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 345, P. 122613 - 122613

Published: April 4, 2024

Language: Английский

Citations

27
Macrophage-derived lncRNAs in cancer: regulators of tumor progression and therapeutic targets DOI
Muath Suliman, Raed Obaid Saleh,

M Chandra

et al.

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(4)

Published: March 6, 2025

Language: Английский

Citations

2
Inhibition of COX-2, mPGES-1 and CYP4A by isoliquiritigenin blocks the angiogenic Akt signaling in glioma through ceRNA effect of miR-194-5p and lncRNA NEAT1 DOI Creative Commons
Chenlong Wang, Yaxin Chen, Yang Wang

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2019, Volume and Issue: 38(1)

Published: Aug. 22, 2019

Arachidonic acid (AA) metabolic enzymes including cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1) and cytochrome P450 (CYP) 4A11 play important roles in glioma angiogenesis. Thus, there is an urgent need to identify the underlying mechanisms develop strategies overcome them.A homology model of human CYP4A11 was constructed using SYBYL-X 2.0. Structure-based virtual screening against COX-2, mPGES-1 CYP4A11was performed Surflex-Dock SYBYL suite. The candidates were further evaluated their antiangiogenic activities a zebrafish embryo rabbit corneal angiogenesis model. Laser doppler analysis used measure tumor perfusion. expression CD31 α-SMA measured by immunofluorescence. Western blot HIF-1, Akt p-Akt. gene FGF-2, G-CSF, PDGF, TGF-β, Tie-2, VEGF, lncRNA NEAT1 miR-194-5p determined qPCR. production TGF-β VEGF analyzed ELISA. Bioinformatic luciferase reporter assays confirmed interaction between miR-194-5p.The nearly 36,043 compounds from Traditional Chinese Medicine (TCM) database screened 3D models, 17 top flavonoids identified. In screening, isoliquiritigenin (ISL) exhibited most potent with EC50 values 5.9 μM. Conversely, effects ISL models partly reversed 20-hydroxyeicosatetraenoic (20-HETE) or E2 (PGE2). normalized vasculature improved efficacy temozolomide therapy rat C6 Inhibition CYP4A decreased U87 cells p-Akt downregulation, which overexpression. Furthermore, downregulated but upregulated cell. Importantly, overexpression ISL-mediated increase expression, thereby attenuated production.Reprogramming mediated-AA metabolism flavonoid inhibits angiogenic Akt- FGF-2/TGF-β/VEGF signaling through ceRNA effect NEAT1, may serve as novel therapeutic strategy for glioma.

Language: Английский

Citations

96
Blocking lncRNA MALAT1/miR-199a/ZHX1 Axis Inhibits Glioblastoma Proliferation and Progression DOI Creative Commons

Keman Liao,

Yingying Lin, Weizhen Gao

et al.

Molecular Therapy — Nucleic Acids, Journal Year: 2019, Volume and Issue: 18, P. 388 - 399

Published: Sept. 17, 2019

Zinc fingers and homeoboxes 1 (ZHX1) is a transcription repressor that has been implicated in the tumorigenesis progression of diverse tumors. The functional role regulating mechanism ZHX1 not elucidated glioblastoma (GBM). Previous reports have suggested large number non-coding RNAs play vital glioma initiation progression. This study aimed to investigate co-regulatory mechanisms metastasis-associated lung adenocarcinoma transcript-1 (MALAT1)/ microRNA-199a (miR-199a)/ZHX1 axis GBM. We analyzed expression MALAT1/miR-199a/ZHX1 its correlation with patients' overall survival using two different gene-expression datasets. A series vitro vivo studies including dual luciferase reporter assay, fluorescence situ hybridization (FISH), RNA immunoprecipitation, pull-down experiments were completed elucidate biological significance promoting proliferation Elevated correlated poor prognosis GBM patients, demonstrated attenuated cell apoptosis by downregulation pro-apoptotic protein (Bax) upregulation anti-apoptotic (Bcl-2). Furthermore, knockdown MALAT1 inhibited reduced tumor volume prolonged an orthotopic murine model. Finally, we promoted via acting as competing endogenous sponging miR-199a. promotes vivo, negatively correlates patient survival. Blocking can serve novel therapeutic strategy for treating

Language: Английский

Citations

93
The Roles of miRNA in Glioblastoma Tumor Cell Communication: Diplomatic and Aggressive Negotiations DOI Open Access
Andrei Buruiană, Ioan Ștefan Florian, Ioan Alexandru Florian

et al.

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

Citations

91