m6A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability

Liu, Hongjiang; Qin, Shan; Liu, Changqi; Jiang, Le; Li, Chen; Yang, Jian; Zhang, Shunyao; Yan, Zhongjie; Liu, Xiaopeng; Yang, Jianhui; Sun, Xiaofang

doi:10.1038/s41420-021-00674-y

Cited by 32 publications

(32 citation statements)

References 21 publications

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“…A study on GBM found that by activating the IGF2BP2/PI3K/Akt axis, IGF2BP2 can significantly promote cell proliferation, migration, invasion, and EMT ( 30 ). Additionally, long noncoding RNA (LncRNA) CASC9 and IGF2BP2 synergistically increases the stability of HK2 mRNA, thereby promoting aerobic glycolysis in GBM ( 31 ). Similarly, IGF2BP2 stabilizes the HK2 and SLC2A1 mRNAs, and accelerates glycolytic metabolism and cell proliferation in colorectal cancer ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Upregulation of IGF2BP2 Promotes Oral Squamous Cell Carcinoma Progression That Is Related to Cell Proliferation, Metastasis and Tumor-Infiltrating Immune Cells

Zhou

Cai

et al. 2022

Front. Oncol.

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The strong invasive and metastatic abilities of oral squamous cell carcinoma (OSCC) cells in the early stage are the main reason for its poor prognosis. The early diagnosis and treatment of OSCC may reduce the metastasis rate and improve the survival rate. The aim of this study was to explore candidate biomarkers related to the prognosis and progression of OSCC. We performed weighted gene coexpression network analysis to identify key modules and genes associated with OSCC and intersected the differentially expressed genes (DEGs) in The Cancer Genome Atlas (TCGA)-OSCC and GSE30784 datasets. Next, we performed survival analysis and immunohistochemistry to screen and validate the hub gene insulin-like growth factor 2 (IGF2) mRNA binding protein 2 IGF2BP2. We also used TCGA pan-cancer data to verify that IGF2BP2 was expressed at high levels in a variety of cancers and was related to a poor prognosis in patients. Furthermore, we divided patients with OSCC into high and low expression groups based on the median expression level of IGF2BP2. Gene set enrichment analysis (GSEA) showed that IGF2BP2 led to a poor prognosis in OSCC by affecting cancer-related (epithelial-mesenchymal transition, glycolysis, cell cycle, etc.) and immune-related biological functions and pathways. Single-sample GSEA (ssGSEA), CIBERSORT, and xCell algorithms helped reveal that high IGF2BP2 expression was accompanied by a significant reduction in the immune score, stromal score, and microenvironment score and a decrease in the number of infiltrating CD8+ T cells in OSCC. In addition, silencing IGF2BP2 suppressed the proliferation, migration, and invasion of OSCC cells. In general, IGF2BP2 is a potential biomarker for the progression, immunotherapy response, and prognosis of OSCC.

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Section: Discussionmentioning

confidence: 99%

Upregulation of IGF2BP2 Promotes Oral Squamous Cell Carcinoma Progression That Is Related to Cell Proliferation, Metastasis and Tumor-Infiltrating Immune Cells

Zhou

Cai

et al. 2022

Front. Oncol.

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“…In prostate cancer, lncRNA PCAT6 interacts with IGF2BP2 to promote bone metastasis by stabilizing insulin-like growth factor1 receptor (IGF1R) mRNA 153 . In glioblastoma, IGF2BP2 recognizes the m 6 A site of lncRNA CASC9 and increases its stability, and CASC9 cooperates with IGF2BP2 to form a complex that stabilizes hexokinase 2 (HK2), promoting aerobic glycolysis 154 . In pancreatic cancer patients, IGF2BP2 is associated with poorer prognosis, and mechanistically, IGF2BP2 plays as m 6 A reader for modification of lncRNA DANCR and stabilizes its mRNA 155 .…”

Section: The Role Of Igf2bps As M 6 a Reader In Ca...mentioning

confidence: 99%

The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m⁶A readers in cancer

Sun¹,

Cao²,

Du³

et al. 2022

Int. J. Biol. Sci.

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RNA can be modified by over 170 types of distinct chemical modifications, and the most abundant internal modification of mRNA in eukaryotes is N6-methyladenosine (m 6 A). The m 6 A modification accelerates mRNA process, including mRNA splicing, translation, transcript stability, export and decay. m 6 A RNA modification is installed by methyltransferase-like proteins (writers), and potentially removed by demethylases (erasers), and this process is recognized by m 6 A-binding proteins (readers). Notably, alterations of m 6 A-modified proteins (writers, erasers and readers) are involved in the tumorigenesis, progression and metastasis. Importantly, the fate of m 6 A-methylated mRNA is mediated mostly through m 6 A readers, and among these readers, insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) are unique RNA-binding proteins (RBPs) that stabilize their targets mRNA via m 6 A modification. In this review, we update the writers, erasers and readers, and their cross-talks in m 6 A modification, and briefly discuss the oncogenic role of IGF2BPs in cancer. Most importantly, we mainly review the up-to-date knowledges of IGF2BPs (IGF2BP1/2/3) as m 6 A readers in an m 6 A-modified manner in cancer progression.

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Section: Lncrnas Interact With Rbps To Regulate the Reprogramming Of ...mentioning

confidence: 99%

“…Insulin-like growth factor 2 mRNA-binding protein (IGF2BP1/2/3, also known as IMP1/2/3) belongs to the K homology domain family and is one of the M 6 A readers involved in the occurrence and development of cancers by interacting with different RNAs ( 50 , 51 ). lncRNA CASC9 has a M 6 A site in glioblastoma multiforme (GBM), which is recognized by IGF2BP2 and enhances the stability of CASC9 ( 52 ). CASC9 interacts with IGF2BP2 to form an IGF2BP2/CASC9 complex, which can bind to the M 6 A modification site of HK2, promote the expression of HK2 by improving the stability of HK2 mRNA, and ultimately promote the Warburg effect ( 52 ).…”

Section: Lncrnas Interact With Rbps To Regulate the Reprogramming Of ...mentioning

confidence: 99%

Research progress on the interaction between long non‑coding RNAs and RNA‑binding proteins to influence the reprogramming of tumor glucose metabolism (Review)

Kong

2022

Oncol Rep

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As epigenetic regulators, long non-coding RNAs (lncRNAs) are involved in various important regulatory processes and typically interact with RNA-binding proteins (RBPs) to exert their core functional effects. An increasing number of studies have demonstrated that lncRNAs can regulate the occurrence and development of cancer through a variety of complex mechanisms and can also participate in tumor glucose metabolism by directly or indirectly regulating the Warburg effect. As one of the metabolic characteristics of tumor cells, the Warburg effect provides a large amount of energy and numerous intermediate products to meet the consumption demands of tumor metabolism, providing advantages for the occurrence and development of tumors. The present review article summarizes the regulatory effects of lncRNAs on the reprogramming of glucose metabolism after interacting with RBPs in tumors. The findings discussed herein may aid in the better understanding of the pathogenesis of malignancies, and may provide novel therapeutic targets, as well as new diagnostic and prognostic markers for human cancers. Contents1. Introduction 2. lncRNAs interact with RBPs to regulate the reprogramming of glucose metabolism in tumor cells through direct action 3. lncRNAs interact with RBPs to regulate the reprogramming of glucose metabolism in tumor cells through indirect action 4. Conclusions and future perspectives

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m6A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability

Cited by 32 publications

References 21 publications

Upregulation of IGF2BP2 Promotes Oral Squamous Cell Carcinoma Progression That Is Related to Cell Proliferation, Metastasis and Tumor-Infiltrating Immune Cells

Upregulation of IGF2BP2 Promotes Oral Squamous Cell Carcinoma Progression That Is Related to Cell Proliferation, Metastasis and Tumor-Infiltrating Immune Cells

The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m⁶A readers in cancer

Research progress on the interaction between long non‑coding RNAs and RNA‑binding proteins to influence the reprogramming of tumor glucose metabolism (Review)

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m6A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability

Cited by 32 publications

References 21 publications

Upregulation of IGF2BP2 Promotes Oral Squamous Cell Carcinoma Progression That Is Related to Cell Proliferation, Metastasis and Tumor-Infiltrating Immune Cells

Upregulation of IGF2BP2 Promotes Oral Squamous Cell Carcinoma Progression That Is Related to Cell Proliferation, Metastasis and Tumor-Infiltrating Immune Cells

The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m6A readers in cancer

Research progress on the interaction between long non‑coding RNAs and RNA‑binding proteins to influence the reprogramming of tumor glucose metabolism (Review)

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The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m⁶A readers in cancer