Non-coding RNAs enhance the apoptosis efficacy of therapeutic agents used for the treatment of glioblastoma multiform

Ghaemi, Shokoofeh; Fekrirad, Zahra; Zamani, Nina; Arefian, Ehsan

doi:10.1080/1061186x.2022.2047191

Cited by 9 publications

(4 citation statements)

References 194 publications

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“…Non-coding RNA molecules (ncRNAs) represent the third major complex of epigenetic regulation. The majority of the entire transcriptome consists of ncRNAs, while protein-coding RNAs make up less than 5% of the transcriptome [ 117 , 118 ]. The three main types of ncRNAs are microRNAs (miRNAs) with a length of about 18–22 nucleotides (nt), long non-coding RNAs (lncRNAs) with a length of >200 nt, and circular RNAs (circRNAs), characterized by a covalent circular bond without 5′-3′ polarity [ 117 , 119 , 120 ].…”

Section: Epigenetic Processesmentioning

confidence: 99%

“…One example is the overexpression of the lncRNA LINC00473 in glioma tissue. This in turn leads to a downregulation of miRNA-195-5p with a reduction of its activity as a tumor suppressor [ 118 , 125 , 127 ]. Other factors, such as EGFR overexpression or EGFRvIII mutations leading to the downregulation of miRNA-524, also have the ability to suppress miRNA activity in gliomas.…”

Section: Epigenetic Processesmentioning

confidence: 99%

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The Spectrum of Molecular Pathways in Gliomas—An Up-to-Date Review

Nafe

Hattingen

2023

Biomedicines

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During the last 20 years, molecular alterations have gained increasing significance in the diagnosis and biological assessment of tumors. Gliomas represent the largest group of tumors of the central nervous system, and the main aim of this review is to present the current knowledge on molecular pathways and their alterations in gliomas. A wide range of new insights has been gained, including evidence for the involvement of the WNT pathway or the hippo pathway in the pathobiology of gliomas, indicating a broad involvement of different pathways formerly not considered to play a central role in gliomas. Even new aspects of angiogenic, apoptotic, and metabolic pathways are presented, as well as the rapidly growing field of epigenetic processes, including non-coding RNAs. The two major conclusions drawn from the present review are the distinct interconnectivity of the whole spectrum of molecular pathways and the prominent role of non-coding RNAs, especially circular RNAs, in the regulation of specific targets. All these new insights are discussed, even considering the topic of the resistance to therapy of gliomas, along with aspects that are still incompletely understood, like the role of hydroxymethylation, or even ferroptosis, in the pathobiology of gliomas.

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Section: Epigenetic Processesmentioning

confidence: 99%

Section: Epigenetic Processesmentioning

confidence: 99%

The Spectrum of Molecular Pathways in Gliomas—An Up-to-Date Review

Nafe

Hattingen

2023

Biomedicines

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“…miRNA detection methods are going to focus on facilitating the development of noninvasive diagnosis and inhibiting cancer drug resistance ( 97 ). In a recent study, the combined use of microRNAs and long noncoding RNAs with chemotherapeutic compounds, as well as the induction of suicide genes, provided an innovative therapeutic approach for the management of glioblastoma (GBM) ( 98 ). It has been reported that miR-532–3p can directly target E26 oncogene homolog 1 (ETS1) and transglutaminase 2 (TGM2) to promote early apoptosis through the ETS1/TGM2 axis-mediated Wnt/β-catenin signaling pathway, and it activates the p53 signaling pathway and enhances the sensitivity to cisplatin and 5-FU in CRC treatment ( 99 ).…”

Section: Future Perspectivesmentioning

confidence: 99%

The role of noncoding RNAs in cancer lipid metabolism

Wang

et al. 2022

Front. Oncol.

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Research on noncoding ribonucleic acids (ncRNAs) is mostly and broadly focused on microRNAs (miRNAs), cyclic RNAs (circRNAs), and long ncRNAs (lncRNAs), which have been confirmed to play important roles in tumor cell proliferation, invasion, and migration. Specifically, recent studies have shown that ncRNAs contribute to tumorigenesis and tumor development by mediating changes in enzymes related to lipid metabolism. The purpose of this review is to discuss the characterized ncRNAs involved in the lipid metabolism of tumors to highlight ncRNA-mediated lipid metabolism-related enzyme expression in malignant tumors and its importance to tumor development. In this review, we describe the types of ncRNA and the mechanism of tumor lipid metabolism and analyze the important role of ncRNA in tumor lipid metabolism and its future prospects from the perspectives of ncRNA biological function and lipid metabolic enzyme classification. However, several critical issues still need to be resolved. Because ncRNAs can affect tumor processes by regulating lipid metabolism enzymes, in the future, we can study the unique role of ncRNAs from four aspects: disease prevention, detection, diagnosis, and treatment. Therefore, in the future, the development of ncRNA-targeted therapy will become a hot direction and shoulder a major task in the medical field.

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“…Numerous long non-coding RNAs (lncRNAs) have been shown to be involved in tumorigenesis [ 1 – 3 ] and apoptosis in cancer cells [ 4 – 10 ]. Several important tumor-suppressive and pro-apoptotic genes, such as p53 and PTEN, are mutated and/or downregulated in various types of cancer [ 11 , 12 ]; on the other hand, numerous pro-apoptotic genes are deficient in cancers [ 8 , 9 , 13 – 16 ], resulting apoptosis resistance and uncontrolled tumor growth.…”

Section: Introductionmentioning

confidence: 99%

The long non-coding RNA keratin-7 antisense acts as a new tumor suppressor to inhibit tumorigenesis and enhance apoptosis in lung and breast cancers

et al. 2023

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Expression of the long non-coding RNA (lncRNA) keratin-7 antisense (KRT7-AS) is downregulated in various types of cancer; however, the impact of KRT7-AS deficiency on tumorigenesis and apoptosis is enigmatic. We aim to explore the influence of KRT7-AS in carcinogenesis and apoptosis. We found that KRT7-AS was deficient in breast and lung cancers, and low levels of KRT7-AS were a poor prognostic factor in breast cancer. Cellular studies showed that silencing of KRT7-AS in lung cancer cells increased oncogenic Keratin-7 levels and enhanced tumorigenesis, but diminished cancer apoptosis of the cancer cells; by contrast, overexpression of KRT7-AS inhibited lung cancer cell tumorigenesis. Additionally, KRT7-AS sensitized cancer cells to the anti-cancer drug cisplatin, consequently enhancing cancer cell apoptosis. In vivo, KRT7-AS overexpression significantly suppressed tumor growth in xenograft mice, while silencing of KRT7-AS promoted tumor growth. Mechanistically, KRT7-AS reduced the levels of oncogenic Keratin-7 and significantly elevated amounts of the key tumor suppressor PTEN in cancer cells through directly binding to PTEN protein via its core nucleic acid motif GGCAAUGGCGG. This inhibited the ubiquitination-proteasomal degradation of PTEN protein, therefore elevating PTEN levels in cancer cells. We also found that KRT7-AS gene transcription was driven by the transcription factor RXRα; intriguingly, the small molecule berberine enhanced KRT7-AS expression, reduced tumorigenesis, and promoted apoptosis of cancer cells. Collectively, KRT7-AS functions as a new tumor suppressor and an apoptosis enhancer in lung and breast cancers, and we unraveled that the RXRα-KRT7-AS-PTEN signaling axis controls carcinogenesis and apoptosis. Our findings highlight a tumor suppressive role of endogenous KRT7-AS in cancers and an important effect the RXRα-KRT7-AS-PTEN axis on control of cancer cell tumorigenesis and apoptosis, and offer a new platform for developing novel therapeutics against cancers.

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Non-coding RNAs enhance the apoptosis efficacy of therapeutic agents used for the treatment of glioblastoma multiform

Cited by 9 publications

References 194 publications

The Spectrum of Molecular Pathways in Gliomas—An Up-to-Date Review

The Spectrum of Molecular Pathways in Gliomas—An Up-to-Date Review

The role of noncoding RNAs in cancer lipid metabolism

The long non-coding RNA keratin-7 antisense acts as a new tumor suppressor to inhibit tumorigenesis and enhance apoptosis in lung and breast cancers

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