China Oncology ›› 2022, Vol. 32 ›› Issue (3): 218-227.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

Diao Xinfeng1, Li Xinmao1, Hou Liang2, Wei Zhixuan1()   

  1. 1. Department of Neurosurgery, the First Affiliated Hospital of Nanyang Medical College, Nanyang 473000, Henan Province, China
    2. Department of Neurosurgery, Wu’an First People’s Hospital, Wu’an 056300, Hebei Province, China
  • Received:2021-11-08 Revised:2021-12-30 Online:2022-03-30 Published:2022-04-02
  • Contact: Wei Zhixuan E-mail:155212056@qq.com

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 P<0.05). Knockdown of YTHDF2 could induce GBM cell cycle arrest and increase apoptotic rate (P<0.05). In GBM cells, YTHDF2 could induce IGFBP7 mRNA decay via recognizing m6A modified IGFBP7 (P<0.05). Inhibition of IGFBP7 partially rescued the effects of si-YTHDF2 on GBM cell cycle and apoptosis (all P<0.05). In addition, YTHDF2 promoted the malignant progression of GBM by regulating IGFBP7 to activate PI3K/AKT signaling pathway (P<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.

Key words: YTHDF2, Glioblastoma, Cell cycle, Cell apoptosis

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