The Potential Value of m6A RNA Methylation in the Development of Cancers Focus on Malignant Glioma

Chen, Fan; Xie, Xuan; Cao, Haiyan; Wang, Liang

doi:10.3389/fimmu.2022.917153

Cited by 9 publications

(5 citation statements)

References 170 publications

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“…Some evidence suggests that m6A alteration may play a key role in gliomas through a variety of mechanisms, providing more opportunities for early diagnosis and targeted therapy of gliomas 2 . Moreover, some m6A based risk score models have also been proposed for predicting the prognosis of glioma patients 32 , 33 . Recently, m6A methylation regulatory genes have been used to classify patients with low-grade gliomas into high- or low-risk subgroups 34 .…”

Section: Discussionmentioning

confidence: 99%

Systematic integration of m6A regulators and autophagy-related genes in combination with long non-coding RNAs predicts survival in glioblastoma multiforme

Sharma,

Wang,

et al. 2023

Sci Rep

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Glioblastoma multiforme (GBM) is probably the only tumor in which a unique epigenetic alteration, namely methylation of the MGMT gene, possesses direct clinical relevance. Now with the emergence of aberrant N6 methyladenosine (m6A) modifications (the most common epigenetic modification of mRNA, closely linked to the autophagy process) in cancer, the epi-transcriptomic landscape of GBM pathobiology has been expanded. Considering this, herein, we systematically analyzed m6A regulators, assessed their correlation with autophagy-related genes (ATG), and established a long non-coding RNAs (lncRNA)-dependent prognostic signature (m6A-autophagy-lncRNAs) for GBM. Our analysis identified a novel signature of five long non-coding RNAs (lncRNAs: ITGA6-AS1, AC124248.1, NFYC-AS1, AC025171.1, and AC005229.3) associated with survival of GBM patients, and four among them clearly showed cancer-associated potential. We further validated and confirmed the altered expression of two lncRNAs (AC124248.1, AC005229.3) in GBM associated clinical samples using RT-PCR. Concerning the prognostic ability, the obtained signature determined high-/low-risk groups in GBM patients and showed sensitivity to anticancer drugs. Collectively, the m6A-autophagy-lncRNAs signature presented in the study is clinically relevant and is the first attempt to systematically predict the potential interaction between the three key determinants (m6A, autophagy, lncRNA) in cancer, particularly in GBM.

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Section: Discussionmentioning

confidence: 99%

Systematic integration of m6A regulators and autophagy-related genes in combination with long non-coding RNAs predicts survival in glioblastoma multiforme

Sharma,

Wang,

et al. 2023

Sci Rep

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“…Isocitrate dehydrogenase (IDH) status is an important basis for molecular typing of gliomas and is reflected in WHO 2016 revised diagnostic criteria ( 7 , 31 ). We further analyzed the differences in inflammatory markers across IDH status in each glioma group to assess their diagnostic value in predicting IDH mutations and wild-type gliomas ( Figure 5 , Figure S3 , Table 4 ).…”

Section: Resultsmentioning

confidence: 99%

“…Glioma is the most common primary brain tumor (3,4), accounting for 81% of CNS tumors (5), and GBM is the most aggressive and most common type of glioma (2). Despite the use of a combination of surgery, radiotherapy, immunotherapy, and Tumor Treating Fields, the 5-year survival rate for GBM is still poor (6)(7)(8)(9). Unlike peripheral cancers, gliomas do not have specific or sensitive serum markers for detecting tumorigenesis, tumor grading, monitoring treatment response, and assessing prognosis (10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

The role of preoperative inflammatory markers in patients with central nervous system tumors, focus on glioma

et al. 2022

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BackgroundCNS tumors, particularly gliomas, are associated with a high rate of disability and lethality, and are typically diagnosed with histopathology and immunohistochemistry. Our research aims to develop a minimally invasive method for diagnosing, grading and molecular typing glioma.MethodsWe collected patients who underwent surgery for glioma, Trigeminal neuralgia/Hemifacial spasm, schwannoma, pituitary adenomas and meningioma at our hospital from June 2019 to June 2021. Preoperative WBCs, neutrophils, lymphocytes, monocytes, platelet counts and albumin levels were collected. Preoperative NLR, dNLR, PLR, LMR and PNI were calculated, and the correlation between them and glioma diagnosis as well as grading was analyzed. We also evaluated the diagnostic significance of NLR, dNLR, PLR, LMR, PNI and their combinations for gliomas, particularly GBM, as well as the diagnostic significance of IDH molecular typing of gliomas.ResultsThere were 182 healthy samples and 3101 diseased samples in our study. Compared with other groups, glioma patients had significantly higher preoperative NLR, dNLR and PLR values, but lower LMR and PNI values. Further analysis showed that NLR, dNLR, and PLR were positively correlated with glioma grading, while LMR and PNI were negatively correlated with glioma grading. For the diagnosis of glioma, NLR showed a maximum AUC value of 0.8099 (0.7823-0.8374). For GBM, NLR showed a maximum AUC value of 0.9585 (0.9467-0.9703). In the combination, NLR+dNLR showed the highest AUC value of 0.8070(0.7849-0.8291). NLR showed significant statistical significance in all grades of glioma IDH molecular typing, while PLR did not show statistical significance.ConclusionsNLR has the greatest value for the diagnosis, differential diagnosis, grading and molecular typing of gliomas. The NLR+dNLR combination also showed high sensitivity and specificity. We believe that inflammatory parameters may serve as economical and specific markers for glioma diagnosis, grading, molecular typing, and progression.

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“…Studies have shown that m6A RNA methylation regulators regulated the proliferation, growth and in ltration of glioma cells. M6A methylation regulation targeted-genes provided reliable support for gliomas [13,29]. Recent studies have found that pyroptosis can promote the occurrence and development of early tumor, which was induced by the up-regulation of HIF-1 α [30].…”

Section: Discussionmentioning

confidence: 98%

METTL3 mediated m6A methylation of HIF-1 α promoted progression in glioma

Wang

Ren

et al. 2023

Preprint

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Background Glioma was a malignant tumor of the central nervous system. m6A methylation and HIF-1α were related to the occurrence and development of gliomas. However, the co-mechanism of m6A methylation and HIF-1α in glioma is unclear. Objective This aim was to determine the m6A methylation of HIF-1α in glioma. Methods Elisa and dot blot were used to detect m6A level. The changes of related genes, biological pathways and gene ontology were analyzed by bioinformatics. METTL3 and HIF-1α were knockdown by sh-RNA, and the mRNA and protein level were detected by qPCR and western blot. In addition, the m6A RNA methylation sites were predicted and verified by m6A-RIP-MMP-6 analysis༎ Results We found that compared with paracancerous, the mRNA and protein levels of m6A were dramatically increased in glioma. The biological different were found in glioma and paracancerous. Moreover, glioma had highly mRNA and protein level of HIF-1α. METTL3 and HIF- 1α knockdown can significantly decrease the growth of glioma cells. Furthermore, we confirmed the m6A RNA methylation site in HIF-1α. Finally, we found that METTL3 regulated the m6A level and RNA stability of HIF-1α. Conclusion Our finding demonstrated that the co-mechanism of m6A methylation of HIF-1α and METTL3 in glioma, and may be helpful in the treatment of glioma.

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The Potential Value of m6A RNA Methylation in the Development of Cancers Focus on Malignant Glioma

Cited by 9 publications

References 170 publications

Systematic integration of m6A regulators and autophagy-related genes in combination with long non-coding RNAs predicts survival in glioblastoma multiforme

Systematic integration of m6A regulators and autophagy-related genes in combination with long non-coding RNAs predicts survival in glioblastoma multiforme

The role of preoperative inflammatory markers in patients with central nervous system tumors, focus on glioma

METTL3 mediated m6A methylation of HIF-1 α promoted progression in glioma

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