N6-methyladenosine (m6A) methyltransferase WTAP accelerates the Warburg effect of gastric cancer through regulating HK2 stability.

N6-methyladenosine (m6A) is one of the most abundant messenger RNAs modification. Increasing evidence illustrates its critical role on gastric cancer. Here, present research focuses on the potential function of m6A methyltransferase Wilms' tumour 1-associated protein (WTAP) in gastric cancer tumorigenesis. Firstly, m6A immunoprecipitation sequencing analysis (MeRIP-Seq) analysis demonstrated the m6A profile in gastric cancer cells. Both WTAP and the m6A expression were up-regulated in gastric cancer tissue and cells. The high-expression of WTAP was closely correlated with poor prognosis of gastric cancer patients. Functional experiments illustrated that WTAP promoted the proliferation and glycolytic capacity (glucose uptake, lactate production and extracellular acidification rate) in vitro, and the knockdown of WTAP suppressed the tumor growth in vivo. Mechanistically, HK2 was identified to be the target of WTAP using MeRIP-Seq and MeRIP-qPCR. WTAP enhanced the stability of HK2 mRNA through binding with the 3'-UTR m6A site. In conclusion, our results demonstrate the oncogenic role of WTAP and its m6A-mediated regulation on gastric cancer Warburg effect, providing a novel approach and therapeutic target in gastric cancer.