N6-methyladenosine reader YTHDF3 contributes to the aerobic glycolysis of osteosarcoma through stabilizing PGK1 stability

Liu, Deyin; Li, Zhong; Zhang, Kun; Lu, Daigang; Zhou, Dawei; Meng, Yibin

doi:10.1007/s00432-022-04337-y

Cited by 9 publications

(8 citation statements)

References 24 publications

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“… 261 In PDAC, YTHDF3-mediated destabilization of lncRNA DICER1-AS1 contributes to enhancing expression of glycolytic genes like LDHA, HK2, PGK1, and SLC2A1, 262 while YTHDF3 targeted m6A-modified PGK1 mRNA to exert a stabilizing role in OS. 263 IGF2BP1 was highly expressed in GC tissue and associated with poor prognosis for GC patients. IGF2BP1 promoted the migration and aerobic glycolysis of GC cells via directly interacting with c-MYC mRNA to stabilize it.…”

Section: Rna Modifications and Cellular Metabolismmentioning

confidence: 95%

RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy

Liu,

Zheng,

et al. 2024

Sig Transduct Target Ther

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Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of cells. Relevant studies have been constantly making inroads in our understanding of pathophysiology, and inspiring development of therapeutics. As a crucial component of epigenetics at post-transcription level, RNA modification significantly determines RNA fates, further affecting various biological processes and cellular phenotypes. To be noted, immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological contexts. In this review, we characterize the distribution features, modifying mechanisms and biological functions of 8 RNA modifications, including N6-methyladenosine (m6A), N6,2′-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N4-acetylcytosine (ac4C), N7-methylguanosine (m7G), Pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing, which are relatively the most studied types. Then regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described, categorized as glucose, lipid, amino acid, and mitochondrial metabolism. And we highlight the regulation of RNA modifications on immunometabolism, further influencing immune responses. Above all, we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy, progression of RNA modification-targeted agents, and its potential in RNA-targeted therapeutics. Eventually, we give legitimate perspectives for future researches in this field from methodological requirements, mechanistic insights, to therapeutic applications.

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Section: Rna Modifications and Cellular Metabolismmentioning

confidence: 95%

RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy

Liu,

Zheng,

et al. 2024

Sig Transduct Target Ther

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“…Besides METTL3, KIAA1429, YTHDF3, METTL16, WTAP, RBM15 and ALKBH5 are identified to regulate OS progression [ 15 , 181 , 185 , 187 , 192 , 201 ]. It is reported that KIAA1429 knockdown decreases the activity of JAK2/STAT3 signal to decreased cell proliferation, migration, and invasion of OS, which can be rescued by JAK2/STAT3 stimulator colivelin [ 188 ].…”

Section: M6a and Skeletal System Diseasementioning

confidence: 99%

“…And KIAA1429 can also act as a crucial gene to regulate Ewing sarcoma progression after CRISPR-Cas9 knockout [ 187 ]. Moreover, researchers found that aerobic glycolysis is essential to make sure OS cells obtain metabolic survival advantage compared with other cells [ 192 ]. Yang et al have proved that circ-CTNNB1 interacted with RBM15 drives aerobic glycolysis and OS progression by elevating key aerobic glycolysis genes expression, such as PGK1 [ 185 ].…”

Section: M6a and Skeletal System Diseasementioning

confidence: 99%

Recent advances of m6A methylation in skeletal system disease

Liang,

Yi,

Liu

et al. 2024

J Transl Med

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Skeletal system disease (SSD) is defined as a class of chronic disorders of skeletal system with poor prognosis and causes heavy economic burden. m6A, methylation at the N6 position of adenosine in RNA, is a reversible and dynamic modification in posttranscriptional mRNA. Evidences suggest that m6A modifications play a crucial role in regulating biological processes of all kinds of diseases, such as malignancy. Recently studies have revealed that as the most abundant epigentic modification, m6A is involved in the progression of SSD. However, the function of m6A modification in SSD is not fully illustrated. Therefore, make clear the relationship between m6A modification and SSD pathogenesis might provide novel sights for prevention and targeted treatment of SSD. This article will summarize the recent advances of m6A regulation in the biological processes of SSD, including osteoporosis, osteosarcoma, rheumatoid arthritis and osteoarthritis, and discuss the potential clinical value, research challenge and future prospect of m6A modification in SSD.

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“…The exact pathogenic mechanisms of osteosarcoma remain largely unclear. It is currently believed to be associated with abnormal expression of certain genes, tumor microenvironment changes, glycolysis and other mechanisms ( Lilienthal & Herold, 2020 ; Liu et al, 2023 ). For example, inactivation of tumor suppressor genes like P53, and overexpression of oncogenes such as c-myc and c-fos can promote the initiation and progression of osteosarcoma ( Li et al, 2021 ; Han et al, 2021 ; Wang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

USP22 as a key regulator of glycolysis pathway in osteosarcoma: insights from bioinformatics and experimental approaches

Zhang,

Zhu,

Xie

et al. 2024

PeerJ

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Background Osteosarcoma is the most common primary malignant bone tumor, but its pathogenesis remains unclear. Ubiquitin-specific processing peptidase 22 (USP22) is reported to be highly expressed and associated with tumor malignancy and prognosis in cancers. However, the role and mechanism of USP22 in osteosarcoma is not fully understood. This study aims to investigate the function and potential mechanism of USP22 in osteosarcoma using bioinformatics analysis combined with experimental validation. Methods We first integrated transcriptomic datasets and clinical information of osteosarcoma from GEO and TCGA databases to assess the expression and prognostic value of USP22 in osteosarcoma. Then, differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify USP22-related co-expressed genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the biological functions and signaling pathways of USP22 co-expressed genes. To validate the accuracy of bioinformatics analyses, we downregulated USP22 expression in osteosarcoma cell line Sao-2 using siRNA and assessed its effect on cell proliferation, migration, invasion, apoptosis, and regulation of key signaling pathways. Results We found that USP22 was highly expressed in osteosarcoma tissues and correlated with poor prognosis in osteosarcoma patients. USP22 also showed potential as a diagnostic marker for osteosarcoma. In addition, 344 USP22-related co-expressed genes were identified, mainly involved in signaling pathways such as glycolysis, oxidative phosphorylation, spliceosome, thermogenesis, and cell cycle. The in vitro experiments confirmed the accuracy and reliability of bioinformatics analyses. We found that downregulation of USP22 could inhibit Sao-2 cell proliferation, migration, invasion, and induce apoptosis. Furthermore, downregulation of USP22 significantly reduced aerobic glycolysis levels in Sao-2 cells and inhibited the expression of key enzymes and transporters in aerobic glycolysis pathways such as HK2, PKM2, and GLUT1. Conclusions USP22 plays a critical role in the occurrence, development, and prognosis of osteosarcoma. USP22 could influence Sao-2 cell proliferation, apoptosis, migration, and invasion by regulating the glycolysis pathway, thereby promoting osteosarcoma progression. Therefore, USP22 may be a potential therapeutic target for the treatment of osteosarcoma.

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N6-methyladenosine reader YTHDF3 contributes to the aerobic glycolysis of osteosarcoma through stabilizing PGK1 stability

Cited by 9 publications

References 24 publications

RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy

RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy

Recent advances of m6A methylation in skeletal system disease

USP22 as a key regulator of glycolysis pathway in osteosarcoma: insights from bioinformatics and experimental approaches

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