Research Spotlight | Newly Discovered Potential Target for Gastric Cancer

2020-11-06Author:adminpraise:0

Scientists from Professor Shouyu Wang’s group recently explored the biological function and clinical significance of METTL3 in gastric cancer (GC).

Congratulations to researchers for publishing the latest articles in the top-level journal "Gut". It is a great honor for Elabscience's products to contribute to this great scientific research achievement. Elabscience is determined to be strict with itself and be the most loyal partner of scientific research scholars!

Fundamental Information:

Title: METTL3-mediated m6A modification of HDGF mRNA promotes gastric cancer progression and has prognostic significance

Journal: Gut

IF19.819 (2020)

Institution of the first author: Nanjing University Medical School, Nanjing, China

Institution of the corresponding author: Nanjing University Medical School, Nanjing, China

Elabscience® Products Cited:

Cat. No

Application

Detection target

Species

Tested sample

E-EL-H5651

ELISA

Human HDGF

Human

Serum


Background of the Research:

Gastric cancer (GC) is the fifth most common neoplasm and the third most deadly cancer worldwide, and almost half of all global GC cases are diagnosed in East Asia. Malignant proliferation and metastasis are found to be first diagnosis in GC patients at an advance stage. Glycolysis and angiogenesis are distinctive features of cancer. Aerobic glycolysis is the primary feature of metabolic reprogramming in cancers and marked by an increase in glucose uptake and preferential lactate production even in the presence of oxygen. It targets glucose transporters and glycolytic enzymes remain an attractive therapeutic intervention. Glycolysis also regulates the tumor microenvironment, and affect inflammatory factor secretion, immune evasion and tumor angiogenesis. Previous study reported that angiogenesis is a key process involved in the proliferation and metastasis of GC. Therfore, understanding the molecular mechanisms of glycolysis and angiogenesis in GC is essential for developing future diagnostic and therapeutic strategies.


Researchers believe that m6A modification in RNA and m6A methyltransferase METTL3 are associated with tumour progression. Specific RNA-binding proteins (also called readers: YTHDF1/2/3, eIF3, IGF2BP1/2/3, HNRNPA2B1 and so on) can bind to the m6A motif directly or indirectly to affect RNA function. The biological significance of m6A and the underlying regulatory mechanisms in human GC have not yet known. In this study the biological role of m6A modification mediated by METTL3 in GC has been studied and it is predicted that METTL3 may be a novel biomarker and therapeutic target for GC development.

Experimental Design:

The prognostic value of METTL3 expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human GC cohort.

The biological role and mechanism of METTL3 in GC tumor growth and liver metastasis were determined in vitro and in vivo.

Research Findings:

1. METTL3 have an oncogenic role in GC development.

2. The level of m6A RNA is significantly increased in GC due to the elevated expression of METTL3.

3. The expression of METTL3 is higher in GC due to P300-mediated activation of H3K27 acetylation, which is associated with poor GC prognosis.

4. METTL3 promotes the m6A modification of HDGF mRNA, and the m6A reader IGF2BP3 directly recognizes and binds to the m6A site on HDGF mRNA and enhances HDGF mRNA stability.

5. The METTL3/ HDGF/GLUT4/ENO2 axis promotes GC tumorigenesis and metastasis via an increase in glycolysis and angiogenesis.

6. METTL3 might be a potential predictor and therapeutic target for GC.

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