关键词: 胶质瘤, N6-甲基腺苷修饰, 有氧糖酵解, 甲基转移酶

Abstract:

Background and purpose: Methyltransferase Wilms’ tumor 1-associating protein (WTAP) has been proven to play an important role in the development of tumors. This study aimed to explore the influence of WTAP on the occurrence and development of glioma from the perspective of N6-methyladenosine (m6A) modification. Methods: The differentially expressed m6A regulators in glioma were screened from GEO database. The expression of WTAP/B cell-specific Moloney murine leukemia virus integration site 1 (BMI1) in glioma tissue and cell lines was evaluated by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot. Methyl thiazoyl terazolium (MTT) was used to explore the effects of WTAP/BMI1 on glioma cell proliferation. Extracellular acidification rate (ECAR) kits and glucose consumption and lactate production detection kits were utilized to detect aerobic glycolysis of glioma cells. Results: Compared with normal tissues, WTQP and BMI1 expressions were upregulated in glioma tissues. Otherwise, compared with WTAP (1.01±0.13) and BMI1 (1.02±0.11) expressions in HEB cells, WTAP (2.38±0.17) and BMI1 (2.25±0.14) expressions in U251 cells were increased (P<0.05). Downregulation of WTAP inhibited cell proliferation and glycolytic potential in vitro, while overexpression of WTAP showed opposite effects. The effects of WTAP overexpression on glioma cell proliferation and glycolysis were partially rescued by BMI1 inhibition (P<0.05). WTAP promoted m6A methylation modification of BMI1 and enhanced the stability of BMI1 mRNA (P<0.05). Conclusion: WTAP upregulates the level of BMI1 in a m6A methylation modification dependent manner, subsequently promotes glioma cell proliferation and aerobic glycolysis. Molecular therapy targeting WTAP may provide a new method for the treatment of glioma.

Key words: Glioma, N6-methyladenosine modification, Aerobic glycolysis, Methyltransferase