Abstract
Methyltransferase-like 3 (METTL3) was originally known to be responsible for N6-methyladenosine (m6A) modification of mRNA. Recent studies have found that METTL3 plays important roles in a variety of tumors by regulating the translation of oncogenes. However, the functional and regulating mechanisms of METTL3 in human gastric cancer have not yet been understood. Here we knocked down METTL3 in human gastric cancer cell lines, AGS and MKN45, by using shRNA transfection. RT-qPCR assay and western blotting verified the effectiveness of RNA interference on mRNA and protein levels, respectively. Then we found that METTL3 knockdown inhibited cell proliferation, migration and invasion in AGS and MKN45 cells. Moreover, METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. Mechanistic investigation suggested that METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and Cyclin D1. In conclusion, our study reveals that down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 may be a potential target for the treatment of human gastric cancer.
Highlights
Gastric cancer is the fifth most common malignancy in the world and approximately 951,600 new cases were diagnosed in 2012 [1]
Through western blotting we demonstrated that down-regulation of Methyltransferase-like 3 (METTL3) increased the expression of Bax and active-casapase-3, while it decreased the expression of Bcl2 (Fig 4A)
Our study has revealed an oncogenic role for METTL3 in human gastric cancer in vitro
Summary
Gastric cancer is the fifth most common malignancy in the world and approximately 951,600 new cases were diagnosed in 2012 [1]. Despite the decline in the death rate due to gastric cancer in recent years, it is still the third leading cause of cancer deaths [2, 3]. Most diagnosed gastric cancer patients are already in the advanced stages, accompanied by malignant hyperplasia, extensive infiltration, lymph node metastasis or distant metastasis [2, 3]. The treatment of gastric cancer is still based on surgical resection and chemotherapy, which leads to many problems such as side effects, recurrence and metastasis [4]. The elucidation of new mechanisms related to the pathogenesis of gastric cancer is crucial for the development of effective targeted therapies for human gastric cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
