The m6A reader IGF2BP3 Facilitates Gastric Cancer Progression Through Activating EMT via Upregulating MYC mRNA Stability

Background: N6-methyladenosine (m6A) RNA methylation plays an important biological role in cancer progression. Even so, the role of m6A modification in gastric cancer (GC) still needs further research. Methods: Firstly, based on the bioinformatics databases and human GC tissues analysis. Secondly, the IGF2BP3 expression in GC cells was measured by the quantificational real-time polymerase chain reaction and Western Blot. Then, the IGF2BP3 knockdown stable cells model was successfully constructed with the specific lentivirus-mediated short-hairpin RNA to explore the functions and mechanism of IGF2BP3 in GC. Next, the functions of IGF2BP3 on the cell phenotypes, including proliferation, invasion, migration, and Epithelial-mesenchymal transition process were clarified by the Cell Counting Kit-8, transwell, and WB experiments. Subsequently, RNA Immunoprecipitation analysis and mRNA stability experiments were used to verify the relationship between IGF2BP3 and MYC. Finally, in the rescue experiment, MYC was overexpressed and transfected into IGF2BP3 knockdown cells to further detect the influences on the cell phenotypes and the EMT process.Results: IGF2BP3 was up-regulated in GC. Meanwhile, IGF2BP3 had diagnostic and prognosis values for GC. Functionally, knockdown IGF2BP3 repressed gastric cancer cells proliferation, migration invasion and EMT process. Mechanically, IGF2BP3 activated the EMT process by improving the expression of MYC via combining with MYC mRNA and promoting its stability. Conclusions: Taken together, IGF2BP3 could activate the EMT process via increasing the MYC mRNA stability and expression to promote GC development, which provided insight into promising early diagnose and treatment for gastric cancer.