Long Non-Coding RNAs in Diagnosis, Treatment, Prognosis, and Progression of Glioma: A State-of-the-Art Review

Momtazmanesh, Sara; Rezaei, Nima

doi:10.3389/fonc.2021.712786

Cited by 35 publications

(31 citation statements)

References 261 publications

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“…LncRNAs are increasingly being investigated for their role in diagnosis, prognosis and treatment of cancers ( 6 ), including gliomas ( 7 ). They are also being investigated for possible role in determining resistance against therapies ( 8 , 9 ), including in gliomas ( 8 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

HOTTIP Mediated Therapy Resistance in Glioma Cells Involves Regulation of EMT-Related miR-10b

Xia

et al. 2022

Front. Oncol.

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The advanced grade glioblastomas are characterized by dismal five-year survival rates and are associated with worse outcomes. Additionally, resistance to therapies is an additional burden responsible for glioma associated mortality. We studied the resistance against temozolomide (TMZ) as a surrogate to understand the mechanism of therapy resistance in glioma cancer cells. Screening of three glioma cells lines, A172, LN229 and SF268 revealed that SF268 glioma cells were particularly resistant to TMZ with the IC-50 of this cell line for TMZ ten times higher than for the other two cell lines. A role of lncRNAs in glioma progression has been identified in recent years and, therefore, we focused on lncRNAs for their role in regulating TMZ resistance in glioma cancer cells. lncRNA HOTTIP was found to be particularly elevated in SF268 cells and over-expression of HOTTIP in both A172 and LN229 remarkably increased their TMZ IC-50s, along with increased cell proliferation, migration, clonogenicity and markers of angiogenesis and metastasis. As a mechanism we observed increased expression of miRNA-10b and mesenchymal markers Zeb1/Zeb2 and reduced expression of E-cadherin in SF268 cells indicating a role of EMT in TMZ resistance. A172 and LN229 cells with overexpressed HOTTIP also had similarly induced EMT and the elevated miR-10b levels. Further, silencing of miR-10b in HOTTIP overexpressing cells as well as the SF268 cells reversed EMT with associated sensitization of all the tested cells to TMZ. Our results thus present a case for HOTTIP in native as well as acquired resistance of glioma cells against chemotherapy, with a key mechanistic role of EMT and the miR-10b. Thus, HOTTIP as well as miR-10b are critical targets for glioma therapy, and need to be tested further.

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Section: Introductionmentioning

confidence: 99%

HOTTIP Mediated Therapy Resistance in Glioma Cells Involves Regulation of EMT-Related miR-10b

Xia

et al. 2022

Front. Oncol.

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“…LncRNAs play crucial regulatory roles in modulating the cell cycle, cell proliferation, cell invasion, and migration by regulating gene expression at the transcriptional, post-transcriptional, and epigenetic levels ( 6 , 7 ). Studies have demonstrated that dysregulation of lncRNA expression is related to gliomas tumorigenesis and cancer progression and that it is a potentially effective early diagnostic, prognostic biomarker, and therapeutic target ( 8 ). However, the specific and detailed molecular mechanisms underlying the involvement of lncRNAs in glioma carcinogenesis and progression remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Molecular Features of Glioma Determined and Validated Using Combined TCGA and GTEx Data Analyses

et al. 2021

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Gliomas are among the most common intracranial tumors which originated from neuroepithelial cells. Increasing evidence has revealed that long noncoding RNA (lncRNA)-microRNA (miRNA)-mRNA module regulation and tumor-infiltrating immune cells play important regulatory roles in the occurrence and progression of gliomas. However, the precise underlying molecular mechanisms remain largely unknown. Data on gliomas in The Cancer Genome Atlas lack normal control samples; to overcome this limitation, we combined 665 The Cancer Genome Atlas glioma RNA sequence datasets with 188 Genotype-Tissue Expression normal brain RNA sequences to construct an expression matrix profile after normalization. We systematically analyzed the expression of mRNAs, lncRNAs, and miRNAs between gliomas and normal brain tissues. Kaplan–Meier survival analyses were conducted to screen differentially expressed mRNAs, lncRNAs, and miRNAs. A prognostic miRNA-related competitive endogenous RNA network was constructed, and the core subnetworks were filtered using 6 miRNAs, 3 lncRNAs, and 11 mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to investigate the biological functions of significantly dysregulated mRNAs. Co-expression network analysis was performed to analyze and screen the core genes. Furthermore, single-sample Gene Set Enrichment Analysis and immune checkpoint gene expression analysis were performed, as co-expression analysis indicated immune gene dysregulation in glioma. Finally, the expression of representative dysregulated genes was validated in U87 cells at the transcriptional level, establishing a foundation for further research. We identified 7017 mRNAs, 437 lncRNAs, and 9 miRNAs that were differentially expressed in gliomas. Kaplan–Meier survival analysis revealed 5684 mRNAs, 61 lncRNAs, and 7 miRNAs with potential as prognostic signatures in patients with glioma. The hub subnetwork of the competing endogenous RNA network between PART1-hsa-mir-25-SLC12A5/TACC2/BSN/TLN2/ZDHHC8 was screened out. Gene co-expression network, single-sample Gene Set Enrichment Analysis, and immune checkpoint expression analysis demonstrated that tumor-infiltrating immune cells are closely related to gliomas. We identified novel potential biomarkers to predict survival and therapeutic targets for patients with gliomas based on a large-scale sample. Importantly, we filtered pivotal genes that provide valuable information for further exploration of the molecular mechanisms underlying glioma tumorigenesis and progression.

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“…A number of studies have indicated that lncRNAs are composed of promoter regions, exons, antisense sequences, enhancer sequences, 3′- and 5′-UTRs, introns, and intergenic and intragenic regions of the genome. LncRNAs have key roles in physiological activities, including epigenetic regulation, cell cycle regulation and cell differentiation regulation through multiple pathways and mechanisms ( 98 ). These RNAs have become a focus of genetic research.…”

Section: Lncrnas and Glioma Drug Resistancementioning

confidence: 99%

“…These RNAs have become a focus of genetic research. More importantly, lncRNAs have been indicated to serve as biomarkers for the diagnosis, treatment, prognostication, drug response prediction and other pathological processes of gliomas by interacting with miRNAs to form a competing endogenous RNA (ceRNA) network, participating in histone modification and directly binding to target genes ( 98 ). In this chapter, the roles of related lncRNAs in the development of chemotherapy resistance in gliomas are discussed and a sufficient theoretical basis for the comprehensive understanding of the mechanisms of tumour drug responses are provided.…”

Section: Lncrnas and Glioma Drug Resistancementioning

confidence: 99%

NcRNAs: Multi‑angle participation in the regulation of glioma chemotherapy resistance (Review)

et al. 2022

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As the most common primary tumour of the central nervous system, gliomas have a high recurrence rate after surgical resection and are resistant to chemotherapy, particularly high-grade gliomas dominated by glioblastoma multiforme (GBM). The prognosis of GBM remains poor despite improvements in treatment modalities, posing a serious threat to human health. At present, although drugs such as temozolomide, cisplatin and bevacizumab, are effective in improving the overall survival of patients with GBM, most patients eventually develop drug resistance, leading to poor clinical prognosis. The development of multidrug resistance has therefore become a major obstacle to improving the effectiveness of chemotherapy for GBM. The ability to fully understand the underlying mechanisms of chemotherapy resistance and to develop novel therapeutic targets to overcome resistance is critical to improving the prognosis of patients with GBM. Of note, growing evidence indicates that a large number of abnormally expressed noncoding RNAs (ncRNAs) have a central role in glioma chemoresistance and may target various mechanisms to modulate chemosensitivity. In the present review, the roles and molecular mechanisms of ncRNAs in glioma drug resistance were systematically summarized, the potential of ncRNAs as drug resistance markers and novel therapeutic targets of glioma were discussed and prospects for glioma treatment were outlined. ncRNAs are a research direction for tumor drug resistance mechanisms and targeted therapies, which not only provides novel perspectives for reversing glioma drug resistance but may also promote the development of precision medicine for clinical diagnosis and treatment.

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Long Non-Coding RNAs in Diagnosis, Treatment, Prognosis, and Progression of Glioma: A State-of-the-Art Review

Cited by 35 publications

References 261 publications

HOTTIP Mediated Therapy Resistance in Glioma Cells Involves Regulation of EMT-Related miR-10b

HOTTIP Mediated Therapy Resistance in Glioma Cells Involves Regulation of EMT-Related miR-10b

Molecular Features of Glioma Determined and Validated Using Combined TCGA and GTEx Data Analyses

NcRNAs: Multi‑angle participation in the regulation of glioma chemotherapy resistance (Review)

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