Long noncoding RNA just proximal to X‐inactive specific transcript facilitates aerobic glycolysis and temozolomide chemoresistance by promoting stability of PDK1 mRNA in an m6A‐dependent manner in glioblastoma multiforme cells

Li, Xu Dong; Wang, Min Jie; Zheng, Jiang; Wu, Yue; Wang, Xuan; Jiang, Xiao Bing

doi:10.1111/cas.15072

Cited by 40 publications

(36 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, upregulation of METTL3 in tumors increases adenylate kinase-4 expression to promote mitochondrial metabolism-mediated tamoxifen resistance and tumor progression [ 213 ]. Similarly, a m 6 A-dependent mechanism enhances PDK1 mRNA stability and mediates temozolomide chemoresistance in glioblastoma by inducing an increase in glycolysis [ 214 ]. The Warburg effect (tumor cell glycolysis) promotes release of glioma exosomes carrying circ_0072083 that upregulates NANOG expression by targeting miR-1252-5p and mediating m 6 A demethylation, thereby promoting temozolomide resistance [ 215 ].…”

Section: A Methylation Regulates the Biological Functions Of Tumor Cellsmentioning

confidence: 99%

Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

et al. 2022

View full text Add to dashboard Cite

The tumor microenvironment (TME), which is regulated by intrinsic oncogenic mechanisms and epigenetic modifications, has become a research hotspot in recent years. Characteristic features of TME include hypoxia, metabolic dysregulation, and immunosuppression. One of the most common RNA modifications, N6-methyladenosine (m6A) methylation, is widely involved in the regulation of physiological and pathological processes, including tumor development. Compelling evidence indicates that m6A methylation regulates transcription and protein expression through shearing, export, translation, and processing, thereby participating in the dynamic evolution of TME. Specifically, m6A methylation-mediated adaptation to hypoxia, metabolic dysregulation, and phenotypic shift of immune cells synergistically promote the formation of an immunosuppressive TME that supports tumor proliferation and metastasis. In this review, we have focused on the involvement of m6A methylation in the dynamic evolution of tumor-adaptive TME and described the detailed mechanisms linking m6A methylation to change in tumor cell biological functions. In view of the collective data, we advocate treating TME as a complete ecosystem in which components crosstalk with each other to synergistically achieve tumor adaptive changes. Finally, we describe the potential utility of m6A methylation-targeted therapies and tumor immunotherapy in clinical applications and the challenges faced, with the aim of advancing m6A methylation research.

show abstract

Section: A Methylation Regulates the Biological Functions Of Tumor Cellsmentioning

confidence: 99%

Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In Glioblastoma (GBM), Li et al recently showed that long noncoding RNA just proximal to X-inactive specific transcript (JPX) interacted with N6-methyladenosine (m 6 A) demethylase FTO and enhanced FTO-mediated PDK1 mRNA demethylation. Additionally, JPX exerted its GBM-promotion effects through the FTO/PDK1 axis (Li et al, 2021). These outcomes reveal the critical role of JPX in promoting GBM aerobic glycolysis-m 6 A demethylase FTO.…”

Section: A Regulates Cancer Metabolismmentioning

confidence: 81%

“…Currently, Li and collaborators demonstrated that the JPX/FTO/ PDK1 axis could facilitate aerobic glycolysis in GBM cells, which was correlated with GBM cells' sensitivity to temozolomide (TMZ). These findings provide valuable information for understanding that blocking the JPX/FTO/PDK1 axis may serve as a promising strategy for mitigating the efficacy of TMZ in GBM (Li et al, 2021). By elucidating the biological roles of m 6 A's modification in natural killer (NK) cells, Ma and collaborators uncovered a new direction for harnessing NK Cell antitumor immunity.…”

Section: Potential Clinical Applications Of M 6 a And Targeting The M...mentioning

confidence: 98%

Interplay Between m6A RNA Methylation and Regulation of Metabolism in Cancer

Mobet

Liu

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Methylation of adenosine in RNA to N6-methyladenosine (m6A) is widespread in eukaryotic cells with his integral RNA regulation. This dynamic process is regulated by methylases (editors/writers), demethylases (remover/erasers), and proteins that recognize methylation (effectors/readers). It is now evident that m6A is involved in the proliferation and metastasis of cancer cells, for instance, altering cancer cell metabolism. Thus, determining how m6A dysregulates metabolic pathways could provide potential targets for cancer therapy or early diagnosis. This review focuses on the link between the m6A modification and the reprogramming of metabolism in cancer. We hypothesize that m6A modification could dysregulate the expression of glucose, lipid, amino acid metabolism, and other metabolites or building blocks of cells by adaptation to the hypoxic tumor microenvironment, an increase in glycolysis, mitochondrial dysfunction, and abnormal expression of metabolic enzymes, metabolic receptors, transcription factors as well as oncogenic signaling pathways in both hematological malignancies and solid tumors. These metabolism abnormalities caused by m6A’s modification may affect the metabolic reprogramming of cancer cells and then increase cell proliferation, tumor initiation, and metastasis. We conclude that focusing on m6A could provide new directions in searching for novel therapeutic and diagnostic targets for the early detection and treatment of many cancers.

show abstract

“…In addition to these classic metabolic enzymes in glycolysis, m6A modification can also regulate some proteins related to glucose metabolism to participate in tumor progression. In GBM, as for temozolomide chemoresistance, JPX can promote the stability of PDK1 through m6A-dependent manner of FTO, thus promoting aerobic glycolysis and promote chemoresistance [ 133 ]. In cervical cancer and liver cancer, PDK4 is involved in glycolysis and ATP generation.…”

Section: The M6a and Metabolicmentioning

confidence: 99%

The role of m6A RNA methylation in cancer metabolism

2022

View full text Add to dashboard Cite

Metabolic reprogramming is one of the main characteristics of malignant tumors, which is due to the flexible changes of cell metabolism that can meet the needs of cell growth and maintain the homeostasis of tissue environments. Cancer cells can obtain metabolic adaptation through a variety of endogenous and exogenous signaling pathways, which can not only promote the growth of malignant cancer cells, but also start the transformation process of cells to adapt to tumor microenvironment. Studies show that m6A RNA methylation is widely involved in the metabolic recombination of tumor cells. In eukaryotes, m6A methylation is the most abundant modification in mRNA, which is involved in almost all the RNA cycle stages, including regulation the transcription, maturation, translation, degradation and stability of mRNA. M6A RNA methylation can be involved in the regulation of physiological and pathological processes, including cancer. In this review, we discuss the role of m6A RNA methylation modification plays in tumor metabolism-related molecules and pathways, aiming to show the importance of targeting m6A in regulating tumor metabolism.

show abstract

Long noncoding RNA just proximal to X‐inactive specific transcript facilitates aerobic glycolysis and temozolomide chemoresistance by promoting stability of PDK1 mRNA in an m6A‐dependent manner in glioblastoma multiforme cells

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 40 publications

References 34 publications

Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

Interplay Between m6A RNA Methylation and Regulation of Metabolism in Cancer

The role of m6A RNA methylation in cancer metabolism

Contact Info

Product

Resources

About