PDGF signaling inhibits mitophagy in glioblastoma stem cells through N-methyladenosine

Lv, Deguan; Gimple, Ryan C.; Zhong, Cuiqing; Wu, Qiulian; Yang, Kailin; Prager, Briana C.; Godugu, Bhaskar; Qiu, Zhixin; Zhao, Linjie; Zhang, Guoxin; Dixit, Deobrat; Lee, Derrick; Shen, Jia; Li, Xiqing; Xie, Qi; Wang, Xiuxing; Agnihotri, Sameer; Rich, Jeremy

doi:10.1016/j.devcel.2022.05.007

Cited by 41 publications

(40 citation statements)

References 53 publications

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“…Mitophagy is also required for self-renewal of human acute myeloid leukemia stem cells 192 . In glioblastoma CSCs, the platelet-derived growth factor (PDGF) signaling inhibits the activation of mitophagy and promotes cancer stem cell maintenance by inducing N 6 -methyladenosine (m 6 A) accumulation 193 . Furthermore, CSCs may also reply on mitophagy to keep low ROS levels and prevent the activation of programmed cell death 194 .…”

Section: Mitochondrial Function In Cancer Stem Cellsmentioning

confidence: 99%

An Overview: The Diversified Role of Mitochondria in Cancer Metabolism

Liu¹,

Sun²,

Guo³

et al. 2023

Int. J. Biol. Sci.

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Mitochondria are intracellular organelles involved in energy production, cell metabolism and cell signaling. They are essential not only in the process of ATP synthesis, lipid metabolism and nucleic acid metabolism, but also in tumor development and metastasis. Mutations in mtDNA are commonly found in cancer cells to promote the rewiring of bioenergetics and biosynthesis, various metabolites especially oncometabolites in mitochondria regulate tumor metabolism and progression. And mutation of enzymes in the TCA cycle leads to the unusual accumulation of certain metabolites and oncometabolites. Mitochondria have been demonstrated as the target for cancer treatment. Cancer cells rely on two main energy resources: oxidative phosphorylation (OXPHOS) and glycolysis. By manipulating OXPHOS genes or adjusting the metabolites production in mitochondria, tumor growth can be restrained. For example, enhanced complex I activity increases NAD + /NADH to prevent metastasis and progression of cancers. In this review, we discussed mitochondrial function in cancer cell metabolism and specially explored the unique role of mitochondria in cancer stem cells and the tumor microenvironment. Targeting the OXPHOS pathway and mitochondria-related metabolism emerging as a potential therapeutic strategy for various cancers.

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Section: Mitochondrial Function In Cancer Stem Cellsmentioning

confidence: 99%

An Overview: The Diversified Role of Mitochondria in Cancer Metabolism

Liu¹,

Sun²,

Guo³

et al. 2023

Int. J. Biol. Sci.

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“…This implies that high levels of m6A could induce anticancer drug resistance. PDGF ligands stimulated early growth response 1 (EGR1) transcription to induce METTL3 to promote glioblastoma stem cells (GSC) proliferation and self-renewal [ 163 ]. Targeting the PDGF-METTL3 axis inhibited mitophagy by decreasing the m6A modification of optineurin (OPTN) in GSCs [ 163 ].…”

Section: The Roles Of Mettl3 In Anticancer Drug Resistance and Autophagymentioning

confidence: 99%

“…PDGF ligands stimulated early growth response 1 (EGR1) transcription to induce METTL3 to promote glioblastoma stem cells (GSC) proliferation and self-renewal [ 163 ]. Targeting the PDGF-METTL3 axis inhibited mitophagy by decreasing the m6A modification of optineurin (OPTN) in GSCs [ 163 ]. Pharmacologic targeting of METTL3 augmented the anti-tumor efficacy of the PDGF receptor (PDGFR) and mitophagy inhibitors in vitro and in vivo [ 163 ].…”

Section: The Roles Of Mettl3 In Anticancer Drug Resistance and Autophagymentioning

confidence: 99%

Roles of RNA Methylations in Cancer Progression, Autophagy, and Anticancer Drug Resistance

Shim

Jeoung

2023

IJMS

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RNA methylations play critical roles in RNA processes, including RNA splicing, nuclear export, nonsense-mediated RNA decay, and translation. Regulators of RNA methylations have been shown to be differentially expressed between tumor tissues/cancer cells and adjacent tissues/normal cells. N6-methyladenosine (m6A) is the most prevalent internal modification of RNAs in eukaryotes. m6A regulators include m6A writers, m6A demethylases, and m6A binding proteins. Since m6A regulators play important roles in regulating the expression of oncogenes and tumor suppressor genes, targeting m6A regulators can be a strategy for developing anticancer drugs. Anticancer drugs targeting m6A regulators are in clinical trials. m6A regulator-targeting drugs could enhance the anticancer effects of current chemotherapy drugs. This review summarizes the roles of m6A regulators in cancer initiation and progression, autophagy, and anticancer drug resistance. The review also discusses the relationship between autophagy and anticancer drug resistance, the effect of high levels of m6A on autophagy and the potential values of m6A regulators as diagnostic markers and anticancer therapeutic targets.

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“…In CESC samples, IGF2BP3 high samples showed higher TJP1, TJP2, CLDN11, CLDN12, MARVELD2, MARVELD3, OCLN, MAGI2, LAMA3, LAMC2, ITGB4 and TJAP1. Discussion m6A RNA modi cation was widely known to have broad effects on malignant tumors by participating in tumor proliferation [30,31], differentiation [32,33], tumorigenesis, invasion and metastasis [34,35], as oncogenes [36] or anti-oncogenes. However, their effects of microbe in cancer formation, prognosis, and treatment have been rarely disputed.…”

Section: Igf2bp3 Was Related To the Tight Junctions In Hpv-related Cescmentioning

confidence: 99%

IGF2BP3 is associated with HPV status and tight junction in HPV-related cervical cancer

Han

Han#

et al. 2023

Preprint

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Background Although m6A modification was known to have broad effects on malignant tumors by participating in tumor proliferation, differentiation, tumorigenesis, invasion and metastasis, as oncogenes or anti-oncogenes, their effects of microbes in cancers have been rarely disputed. To investigate the function of IGF2BP3, one of the indispensable regulators of m6A, in HPV virus invading and transmitting, integrative analyses was performed in this study and identified that it was highly expressed in tumors and was related to the poor prognosis in CESC. Methods We investigate the expresseion level of IGF2BP3 and its prognostic value in CESC via multiple datasets including TCGA, GTEx datasets and TIMER. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of differentially expressed genes were performed using GOplot, org.Hs.eg.db and clusterProfiler packages and visualized using the ggplot2 package Results In HPV-positive tumors, IGF2BP3 was positively associated with tumor HPV status. Further analysis demonstrated that IGF2BP3 high status was correlated with signaling pathways related to cell-cell and cell-ECM interactions, including receptor ligand activity, neuroactive ligand receptor interaction and chemical carcinogenesis receptor activation. Moreover, correlation analysis showed that IGF2BP3 would impair the formation of cell polarity and cell-cell contacts by dysregulating the expression of tight junction molecules. Conclusions Our results identified that IGF2BP3 high status, is associated with poor prognosis and HPV status, and IGF2BP3 serves as a mediator of the tight junction formation in HPV-associated cancer, which provides a promising therapeutic target for anti-cancer schedule.

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PDGF signaling inhibits mitophagy in glioblastoma stem cells through N-methyladenosine

Cited by 41 publications

References 53 publications

An Overview: The Diversified Role of Mitochondria in Cancer Metabolism

An Overview: The Diversified Role of Mitochondria in Cancer Metabolism

Roles of RNA Methylations in Cancer Progression, Autophagy, and Anticancer Drug Resistance

IGF2BP3 is associated with HPV status and tight junction in HPV-related cervical cancer

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