N6-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification.

Abstract

N6-methyladenosine (m6A) serves as the most common and conserved internal transcriptional modification. However, the roles of m6A on cervical cancer (CC) tumorigenesis are still unclear. Here, results indicated that METTL3 was significantly upregulated in CC tissue and cells, which was closely correlated with the lymph node metastasis and poor prognosis of CC patients. MeRIP-Seq analysis revealed the m6A profiles in CC cells. Functionally, METTL3 promoted the proliferation and Warburg effect (aerobic glycolysis) of CC cells. Mechanistically, METTL3 targeted the 3'-Untranslated Region (3'-UTR) of hexokinase 2 (HK2) mRNA. Moreover, METTL3 recruited YTHDF1, a m6A reader, to enhance HK2 stability. These findings demonstrated that METTL3 enhanced the HK2 stability through YTHDF1-mediated m6A modification, thereby promoting the Warburg effect of CC, which might promote a novel insight for the CC treatment.

• Authors: Qianqing Wang, Xiangcui Guo, Li Li, Zhihui Gao, Xiaoke Su, Mei Ji, Juan Liu
• Journal: Cell death & disease (Cell Death Dis) Vol. 11 Issue 10 Pg. 911 (10 24 2020) ISSN: 2041-4889 [Electronic] England
• PMID: 33099572 (Publication Type: Journal Article)

Chemical References

• RNA-Binding Proteins
• YTHDF1 protein, human
• N-methyladenosine
• Methyltransferases
• METTL3 protein, human
• HK2 protein, human
• Hexokinase
• Adenosine

Topics

• Adenosine (analogs & derivatives, metabolism)
• Animals
• Carcinogenesis
• Cell Line, Tumor
• Cell Proliferation (physiology)
• Female
• Heterografts
• Hexokinase (metabolism)
• Humans
• Male
• Methyltransferases (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• Prognosis
• RNA-Binding Proteins (metabolism)
• Transfection
• Uterine Cervical Neoplasms (metabolism, pathology)
• Warburg Effect, Oncologic