Glioblastoma Multiforme: Pathogenesis and Molecular Markers

Circular RNAs (circRNAs) are an evolutionarily conserved novel class of non-coding endogenous RNAs (ncRNAs) found in the eukaryotic transcriptome, originally believed to be aberrant RNA splicing by-products with limited functionality. However, recent advances in highthroughput genomic technology have allowed circRNAs to be characterized in detail and revealed their important functions in controlling various biological and molecular processes, the most essential being gene regulation. Due to structural stability, high expression, availability of microRNA (miRNA) binding sites and tissue-specific expression, circRNAs have become hot topic of research in RNA 2 biology. Unlike linear RNAs, circRNAs are produced differentially by backsplicing exons or lariat introns from a pre-messenger RNA (mRNA) forming covalently closed loop-like molecules missing 3' poly-(A) tail or 5' cap structures, thus rendering them resistant to exonuclease-mediated degradation. Previous studies have revealed multiple roles of circRNAs as sponges for miRNA and RNA-binding proteins (RBP), as well as regulators of transcription, translation, and splicing events. Recent advances in the field suggest that the circRNAs are involved in many human disorders, including cancer and neurodegenerative disorders such as Alzheimers and Parkinsons disease, due to their aberrant expression in different pathological conditions. The circRNAs are stable in cells, owing to their circular structure. Participation of circRNAs in programmed cellular destruction by autophagy is discussed in details. The autophagy is a catabolic process which promotes decomposition and recycling of harmful or redundant biological macromolecules and initiates destruction of ageing cells. Processes how circRNAs influence a course of a disease, including an autophagy are in detail discussed, specifying that it joins at the beginning and upon development of various illnesses, and it can influence drug resistance (for example, antitumor efficiency of Cisplatin). The functional versatility exhibited by circRNAs enables them to serve as potential diagnostic or predictive biomarkers for various diseases. This review discusses the properties, characterization, profiling, and the diverse molecular actions of circRNAs and their usage as potential therapeutic targets in different human malignancies.

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Circular RNAs in eukaryotic cells: origin, characteristics, mechanisms of molecular functioning in human malignant diseases

Vashchenko

Chuklovin

Shabanov

2023

Rev Clin Pharm Drug Ther

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Growth and Molecular Characteristics of Temozolomide-Resistant Human A172 and R1 Glioblastoma Cells

Pinevich,

Vartanyan,

Kartashev

et al. 2023

Citologiâ

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Glioblastoma recurrence is caused by initial and acquired as a result of therapy resistance of tumor cells. Studies searching the markers that would allow predicting the level of glioblastoma cell resistance to therapy are in progress. The complexity of the problem is related to the high heterogeneity of individual tumors and the cellular content of each tumor. In present work, a comparative study of the influence of single temozolomide (in Temodal® form) ex-posure on the well-known glioblastoma cell line A172 and a new one R1 was performed. In A172 (highly tem-ozolomide-sensitive cell line) after treatment with 0.1 mM of this drug only individual cells persisted and resumed proliferation. In R1 glioblastoma cell line single cells survived and resumed proliferation after treatment with 1 mM temozolomide. The populations resulting from the proliferation of these cells were designated as resistant. The expression of MGMT, as well as genes responsible for resistance to chemotherapy and tumor progression (MGMT, ABCB1, ABCC1, ABCG2), growth factor genes (VEGF, HGF), cytokines IL-6 and IL-8, and their encoding genes was examined in resistant A172 and R1 cells. In A172 cells, the methylated status of MGMT gene promoter was confirmed, as well as the absence of the corresponding gene expression. It was shown for the first time that glioblastoma R1 is heterogeneous by the methylation status of MGMT gene promoter and expression of the relevant enzyme. In A172 and R1 resistant cell populations, the level of MGMT gene promoter methylation was lower than in the intact cells, and MGMT gene expression was enhanced. We suspect that this may be the reason for greater resistance of such cells to chemotherapy. The expression of most genes associated with resistance to chemotherapy and a more aggressive course of the disease, genes of growth factors, and interleukins in resistant A172 cells was higher than in intact cells. In contrast, in resistant R1 cells, the expression of most of the same genes (with the exception of ABCC1 and VEGF, for which the expression level changed insignificantly) was lower than in the intact cells. These results confirm the significance of MGMT in the formation of glioblastoma cell resistance to temozolomide. The prognostic value of the other studied parameters is still ambiguous.

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Glioblastoma Multiforme: Pathogenesis and Molecular Markers

Cited by 2 publications

References 34 publications

Circular RNAs in eukaryotic cells: origin, characteristics, mechanisms of molecular functioning in human malignant diseases

Circular RNAs in eukaryotic cells: origin, characteristics, mechanisms of molecular functioning in human malignant diseases

Growth and Molecular Characteristics of Temozolomide-Resistant Human A172 and R1 Glioblastoma Cells

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