METTL3 Expression Influences Gastric-Cancer Progression

By Will Boggs MD

December 04, 2019

NEW YORK (Reuters Health) - Increased expression of METTL3 independently predicts gastric-cancer progression and could represent a therapeutic target, researchers from China report.

"Our study demonstrated that METTL3 may be used as an early prognostic biomarker for gastric-cancer patients and a predictive biomarker for their survival," Dr. Shouyu Wang from The Affiliated Drum Tower Hospital of Nanjing University Medical School told Reuters Health by email. "Now METTL3-specific inhibitors are under investigation, which may be beneficial for METTL3-positive gastric-cancer patients."

METTL3, through its methylation of N6-methyladenosine, has been shown to be involved in tumor initiation and progression.

Dr. Wang's team evaluated the biological role and mechanism of METTL3 in gastric-cancer tumor growth and liver metastasis in vitro and in vivo.

METTL3 expression was significantly upregulated in gastric-cancer tissues compared with paired normal gastric mucosa. And patients with increased METTL3 expression had a 4.5-fold increased risk of five-year mortality, the researchers report in Gut, online October 3.

In vitro, METTL3 overexpression was associated with gastric-cancer cell proliferation and increased microvessel density, a marker of angiogenesis.

Moreover, METTL3 promoted gastric-cancer metastasis both in vitro and in vivo.

METTL3 appeared to accelerate the malignant process by upregulating expression of hepatoma-derived growth factor and the resultant increase in glycolysis and angiogenesis.

"As we know, DNA mutation and protein modification play key roles in tumor progression," Dr. Wang said. "However, we also should pay more attention to the epigenetics and tumor metabolism in gastric-cancer development and progression."

The study did not have commercial funding.


Gut 2019.