YTHDF2 promotes progression of glioblastoma via inducing mRNA decay of IGFBP7 and activating PI3K/AKT signaling pathway

Xinfeng Diao; Xinmao Li; Liang Hou; Zhixuan Wei

doi:10.19401/j.cnki.1007-3639.2022.03.004

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YTHDF2 promotes progression of glioblastoma via inducing mRNA decay of IGFBP7 and activating PI3K/AKT signaling pathway

Article | 更新时间：2025-12-31

- YTHDF2 promotes progression of glioblastoma via inducing mRNA decay of IGFBP7 and activating PI3K/AKT signaling pathway
- China Oncology Vol. 32, Issue 3, Pages: 218-227(2022)
- 作者机构：
  
  1. 南阳医学高等专科学校第一附属医院神经外科,河南南阳 473000
  2. 武安市第一人民医院神经外科,河北武安 056300
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2022.03.004
  CLC： R739.41
- Received：08 November 2021，
  
  Published：30 March 2022
- 稿件说明：
移动端阅览
Xinfeng Diao, Xinmao Li, Liang Hou, et al. YTHDF2 promotes progression of glioblastoma via inducing mRNA decay of IGFBP7 and activating PI3K/AKT signaling pathway[J]. China Oncology, 2022, 32(3): 218-227.
DOI：

Xinfeng Diao, Xinmao Li, Liang Hou, et al. YTHDF2 promotes progression of glioblastoma via inducing mRNA decay of IGFBP7 and activating PI3K/AKT signaling pathway[J]. China Oncology, 2022, 32(3): 218-227. DOI： 10.19401/j.cnki.1007-3639.2022.03.004.

摘要

背景与目的：

N6-甲基腺苷（N6-methyladenosine

m6A）甲基化修饰识别蛋白YTHDF2被证实在癌症进展中扮演重要角色。探讨YTHDF2是否通过促进胰岛素样生长因子结合蛋白7（insulin-like growth factor binding protein 7

IGFBP7）的mRNA衰变

激活磷脂酰肌醇3-激酶（phosphoinositide 3-kinase

PI3K）-蛋白激酶B（protein kinase

AKT）信号转导通路

调控胶质母细胞瘤（glioblastoma

GBM）的细胞周期和凋亡。

方法：

采用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction

RTFQ-PCR）检测YTHDF2和IGFBP7在GBM组织和细胞中的表达。通过流式细胞术检测细胞周期和凋亡率。采用蛋白质印迹法（Western blot）检测p-AKT、AKT、p-PI3K和PI3K蛋白表达。采用RNA免疫沉淀（RNA immunoprecipitation

RIP）实验和RNA稳定性实验验证YTHDF2与IGFBP7之间的关系。

结果：

与癌旁组织和正常星形胶质细胞系（NHA细胞）相比

YTHDF2在GBM组织和细胞中表达升高

IGFBP7表达降低（

均

0.05）。敲减YTHDF2可诱导GBM细胞周期阻滞和凋亡率升高（

0.05）。在GBM细胞中

YTHDF2可通过识别m6A修饰的IGFBP7进而促进IGFBP7 mRNA降解（

0.05）。抑制IGFBP7可部分地挽救si-YTHDF2对GBM细胞周期和凋亡的影响（

均

0.05）。此外

YTHDF2还可通过调控IGFBP7激活PI3K/AKT信号转导通路促进GBM恶性进展（

0.05）。

结论：

YTHDF2通过m6A修饰的方式调控IGFBP7的表达

激活PI3K/AKT信号转导通路以促进GBM细胞恶性生物学行为。

Abstract

Background and purpose:

N6-methyladenosine (m6A) methylation modification recognition protein YTHDF2 has been shown to play an important role in cancer progression. This research was designed to explore whether YTHDF2 regulated cell cycle and apoptosis of glioblastoma (GBM) via promoting mRNA decay of insulin-like growth factor binding protein 7 (IGFBP7) and activating phosphoinositide 3-kinase (PI3K)-protein kinase (AKT) signaling pathway.

Methods:

The expressions of YTHDF2 and IGFBP7 in GBM tissues and cells were detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). The cell cycle and apoptosis rate were detected by flow cytometry. Protein expressions of p-AKT

AKT

p-PI3K and PI3K were detected by Western blot. RNA immunoprecipitation (RIP) assay and RNA stability experiment were used to verify the relationship between YTHDF2and IGFBP7.

Results:

Compared with adjacent tissues and normal astrocyte line (NHA cells) expression of YTHDF2 was increased while expression of IGFBP7 was decreased in GBM tissues and cells (all

0.05). Knockdown of YTHDF2 could induce GBM cell cycle arrest and increase apoptotic rate (

0.05). In GBM cells

YTHDF2 could induce IGFBP7 mRNA decay via recognizing m6A modified IGFBP7 (

0.05). Inhibition of IGFBP7 partially rescued the effects of si-YTHDF2 on GBM cell cycle and apoptosis (all

0.05). In addition

YTHDF2 promoted the malignant progression of GBM by regulating IGFBP7 to activate PI3K/AKT signaling pathway (

0.05).

Conclusion:

YTHDF2 promotes the malignant biological behavior of GBM cells through regulating IGFBP7 expression by means of m6A modification and activating PI3K/AKT signaling pathway.

关键词

Keywords

references

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