Long Non-Coding RNAs in Gliomas: From Molecular Pathology to Diagnostic Biomarkers and Therapeutic Targets

Večeřa, Marek; Šána, Jiří; Lipina, Radim; Smrčka, Martin; Slabý, Ondřej

doi:10.3390/ijms19092754

Cited by 31 publications

(25 citation statements)

References 70 publications

(78 reference statements)

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“…Accurate and timely diagnosis of brain glioma and targeted treatment plans are the current challenges in the treatment of glioma. With the continuous expansion and deepening of clinical research, biological markers and molecular pathology can facilitate the diagnosis and treatment of various diseases [4]. Given the limitations in the diagnosis of glioma, the pathological tumor types, tumor biological behaviors, prognosis, and postoperative clinical treatment of patients with glioma remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Joint bioinformatics analysis of underlying potential functions of hsa-let-7b-5p and core genes in human glioma

Chu

Liu

et al. 2019

J Transl Med

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Background: Glioma accounts for a large proportion of cancer, and an effective treatment for this disease is still lacking because of the absence of specific driver molecules. Current challenges in the treatment of glioma are the accurate and timely diagnosis of brain glioma and targeted treatment plans. To investigate the diagnostic biomarkers and prospective role of miRNAs in the tumorigenesis and progression of glioma, we analyzed the expression of miRNAs and key genes in glioma based on The Cancer Genome Atlas database. Methods: Of the 701 cases that were downloaded, five were normal and 696 were glioma. Then, 1626 differentially expressed genes were identified, and 173 aberrantly expressed miRNAs were calculated by edgeR. GO and KEGG pathway enrichment analyses were performed using Cytoscape software. A coexpression network was built by weighted correlation network analysis (WGCNA). A cell scratch test and transwell, cell apoptosis and cell cycle assays were performed to validate the function of hsa-let-7b-5p. Results: Based on crosstalk genes in the KEGG, PPI network, and WGCNA analyses, PLK1, CCNA2, cyclin B2 (CCNB2), and AURKA were screened as candidate diagnostic marker genes. The survival analysis revealed that high mRNA expression of PLK1, CCNA2, and AURKA was significantly associated with poor overall survival. Furthermore, hsalet-7b-5p was identified as a core miRNA in the regulation of candidate genes involved in glioma development. We confirmed that hsa-let-7b-5p could inhibit the migration, invasion, and cell cycle of glioma cells. Conclusions: This study provides four potential biomarkers for the diagnosis of glioma, offers a potential explanation of its pathogenesis, and proposes hsa-let-7b-5p as a therapeutic target.

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Section: Introductionmentioning

confidence: 99%

Joint bioinformatics analysis of underlying potential functions of hsa-let-7b-5p and core genes in human glioma

Chu

Liu

et al. 2019

J Transl Med

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“…It has been identified that lncRNAs play important roles in the diagnosis, prognosis and treatment of glioma [26]. However, the mechanisms underpinning the involvement of lncRNA KCNQ1OT1 in glioma progression remain to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of lncRNA KCNQ1OT1 inhibits glioma progression by regulating miR-338-3p/RRM2

et al. 2020

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AbstractThe dysregulated lncRNA play essential roles in glioma development. This study aimed to investigate the role and mechanism of lncRNA potassium voltage-gated channel subfamily Q member 1 opposite strand/ antisense transcript 1 (KCNQ1OT1) in glioma progression. Tumor tissues and adjacent normal samples were collected from 30 glioma patients. The expression levels of lncRNA KCNQ1OT1, microRNA (miR)-338-3p and ribonucleotide reductase M2 (RRM2) were detected by quantitative real-time polymerase chain reaction or western blot analyses. Levels of cell viability, apoptosis, cell migration and invasion in glioma cell lines were determined using cell counting kit-8, flow cytometry with annexin V-FITC and trans-well assays, respectively. The role of KCNQ1OT1 in glioma development in vivo was investigated using a xenograft model. The target association between miR-338-3p and KCNQ1OT1 or RRM2 was validated by luciferase reporter assay. The results found that expression of KCNQ1OT1 was enhanced in glioma tissues and cells, and KCNQ1OT1 knockdown inhibited cell viability, migration and invasion, and xenograft tumor growth, but promoted apoptosis. miR-338-3p was targeted via KCNQ1OT1 and could reverse the effect of KCNQ1OT1 on glioma progression. RRM2 was targeted via miR-338-3p and attenuated the suppressive effect of miR-338-3p on glioma cell viability, migration and invasion. Besides, KCNQ1OT1 overexpression increased RRM2 expression, and this event was weakened via miR-338-3p up-regulation. In conclusion, the present finding suggest that silencing of KCNQ1OT1 can suppress the development and progression of glioma by up-regulating miR-338-3p and down-regulating RRM2.

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“…Long noncoding RNAs (lncRNA) namely HOX transcript antisense RNA (HOTAIR), nuclear enriched abundant transcript 1 (NEAT1), and maternally expressed gene 3 were negatively associated; differentiation antagonizing non-protein coding RNA (DANCR) was found to be positively affecting GBM progression through Wnt activation [61].…”

Section: Role Of Wnt Signaling Pathway In Glioblastoma and Developmenmentioning

confidence: 99%

Glioblastoma stem cells and Wnt signaling pathway: molecular mechanisms and therapeutic targets

2020

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Glioblastoma is the most common form of primary brain tumor. Glioblastoma stem cells play an important role in tumor formation by activation of several signaling pathways. Wnt signaling pathway is one such important pathway which helps cellular differentiation to promote tumor formation in the brain. Glioblastoma remains to be a highly destructive type of tumor despite availability of treatment strategies like surgery, chemotherapy, and radiation. Advances in the field of cancer biology have revolutionized therapy by allowing targeting of tumor-specific molecular deregulation. In this review, we discuss about the significance of glioblastoma stem cells in cancer progression through Wnt signaling pathway and highlight the clinical targets being potentially considered for therapy in glioblastoma.

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Long Non-Coding RNAs in Gliomas: From Molecular Pathology to Diagnostic Biomarkers and Therapeutic Targets

Cited by 31 publications

References 70 publications

Joint bioinformatics analysis of underlying potential functions of hsa-let-7b-5p and core genes in human glioma

Joint bioinformatics analysis of underlying potential functions of hsa-let-7b-5p and core genes in human glioma

Knockdown of lncRNA KCNQ1OT1 inhibits glioma progression by regulating miR-338-3p/RRM2

Glioblastoma stem cells and Wnt signaling pathway: molecular mechanisms and therapeutic targets

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