Dataset Information

M⁶A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability.

ABSTRACT: N⁶-methyladenosine (m⁶A) has been identified to exert critical roles in human cancer; however, the regulation of m⁶A modification on glioblastoma multiforme (GBM) and long non-coding RNA (lncRNA) CASC9 (cancer susceptibility 9) is still unclear. Firstly, MeRIP-Seq revealed the m⁶A profile in the GBM. Moreover, the m⁶A-related lncRNA CASC9 expression was significantly elevated in the GBM tissue and its ectopic high expression was associated with poor survival, acting as an independent prognostic factor for GBM patients. Functionally, the aerobic glycolysis was promoted in the CASC9 overexpression transfection, which was inhibited in CASC9 knockdown in GBM cells. Mechanistically, m⁶A reader IGF2BP2 (insulin-like growth factor 2 mRNA binding protein 2) could recognize the m⁶A site of CASC9 and enhance its stability, then CASC9 cooperated with IGF2BP2, forming an IGF2BP2/CASC9 complex, to increase the HK2 (Hexokinase 2) mRNA stability. Our findings reveal that CASC9/IGF2BP2/HK2 axis promotes the aerobic glycolysis of GBM.

SUBMITTER: Liu H

PROVIDER: S-EPMC8514511 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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

Liu Hongjiang H Qin Shan S Liu Changqi C Jiang Le L Li Chen C Yang Jiankai J Zhang Shunyao S Yan Zhongjie Z Liu Xiaopeng X Yang Jipeng J Sun Xiaofeng X

Cell death discovery 20211013 1

N6-methyladenosine (m6A) has been identified to exert critical roles in human cancer; however, the regulation of m6A modification on glioblastoma multiforme (GBM) and long non-coding RNA (lncRNA) CASC9 (cancer susceptibility 9) is still unclear. Firstly, MeRIP-Seq revealed the m6A profile in the GBM. Moreover, the m6A-related lncRNA CASC9 expression was significantly elevated in the GBM tissue and its ectopic high expression was associated w ...[more]

PMID: 34645788

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Project description:Background Aerobic glycolysis has been recognized as one of the growth-promoting metabolic alterations of cancer cells. Emerging evidence indicates that nuclear factor κB (NF-κB) plays significant roles in metabolic adaptation in normal cells and cancer cells. However, whether and how NF-κB regulates metabolic reprogramming in hepatocellular carcinoma (HCC), specifically hepatitis B virus X protein (HBx)-initiated HCC, has not been determined. Methods A dataset of the HCC cohort from the TCGA database was used to analyse the expression of NF-κB family members. Expression of NF-κBp65 and phosphorylation of NF-κBp65 (p-p65) were detected in liver tissues from HBV-related HCC patients and normal controls. A newly established HBx+/+/NF-κBp65f/f and HBx+/+/NF-κBp65Δhepa spontaneous HCC mouse model was used to investigate the effects of NF-κBp65 on HBx-initiated hepatocarcinogenesis. Whether and how NF-κBp65 is involved in aerobic glycolysis induced by HBx in hepatocellular carcinogenesis were analysed in vitro and in vivo. Results NF-κBp65 was upregulated in HBV-related HCC, and HBx induced NF-κBp65 upregulation and phosphorylation in vivo and in vitro. Hepatocyte-specific NF-κBp65 deficiency remarkably decreased HBx-initiated spontaneous HCC incidence in HBx-TG mice. Mechanistically, HBx induced aerobic glycolysis by activating NF-κBp65/hexokinase 2 (HK2) signalling in spontaneous hepatocarcinogenesis, and overproduced lactate significantly promoted HCC cell pernicious proliferation via the PI3K (phosphatidylinositide 3-kinase)/Akt pathway in hepatocarcinogenesis. Conclusion The data elucidate that NF-κBp65 plays a pivotal role in HBx-initiated spontaneous HCC, which depends on hyperactive NF-κBp65/HK2-mediated aerobic glycolysis to activate PI3K/Akt signalling. Thus, phosphorylation of NF-κBp65 will be a potential therapeutic target for HBV-related HCC. Supplementary Information The online version contains supplementary material available at 10.1186/s13046-022-02531-x.

Dataset Information

M⁶A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability.

Publications

m<sup>6</sup>A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability.

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Dataset Information

M6A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability.

Publications

m<sup>6</sup>A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

M⁶A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability.