METTL3 Regulates CRNDE Methylation And Mediates The Role And Mechanism Of Hippo Pathway In Pancreatic Cancer

BACKGROUND:Pancreatic cancer is a highly malignant gastrointestinal tumor.The pathogenesis of it has not been fully elucidated,which affects the development of diagnosis and treatment of pancreatic cancer.Therefore,the study of the molecular mechanism of pancreatic cancer occurrence and development is significant,which can improve the diagnosis and prognosis of pancreatic cancer.As a long non-coding RNA,CRNDE is highly expressed in a variety of cancers and closely related to the development of cancer.However,the regulatory mechanism of CRNDE in pancreatic cancer is still unclear.Previous research by our research group confirmed that CRNDE can regulate the activation process of Hippo pathway and mediate the occurrence and development of pancreatic cancer,but its specific regulatory mechanism is still unclear.Studies have reported that in non-small cell lung cancer,METTL3 can upregulate YAP protein expression by regulating MALAT1,thereby inducing tumor resistance and malignant metastasis.We speculated that METTL3 may indirectly regulate the Hippo pathway through a similar pathway in pancreatic cancer.That is METTL3 can regulate the Hippo pathway through regulating the expression of CRNDE to mediate the occurrence and development of pancreatic cancer.RESEARCH PURSOSES:This study focused on the role and mechanism of METTL3 regulating CRNDE m~6A-methylation-mediated Hippo pathway in pancreatic cancer.This study aimed to elucidate whether METTL3 can affect the Hippo pathway through the m~6A methylation of CRNDE and promote the occurrence and development of pancreatic cancer.METHODS:This study first examined the expression of METTL3 in pancreatic cancer tissues and cells;Then,CCK8,flow cytometry,Transwell were conducted to the study the effect of METTL3 expression on the proliferation,apoptosis and invasion of pancreatic cancer cells;Finally,the real-time quantitative RT-PCR technology and western blot were used to study the regulatory role between METTL3 and CRNDE,and the effect of METTL3 expression on the expression of core molecules in the Hippo pathway.RESULTS:This study found that METTL3 was highly expressed in pancreatic cancer tissues and pancreatic cancer cells;Then,we confirmed that METTL3 can promote pancreatic cancer cells'ability of proliferation,invasion,and inhibit cell apoptosis in vitro;We also found that METTL3 had a regulatory effect on CRNDE;Finally,we transfected siRNA-METTL3 into pancreatic cancer cells,and the results showed that after METTL3 expression was down-regulated,the expression of oncogene YAP/TAZ in the Hippo pathway was significantly reduced,indicating that METTL3 can inhibit the activation of the Hippo pathway.Couclusion:This article initially confirmed the important role of METTL3 in the development of pancreatic cancer.METTL3 can regulate the Hippo pathway through the m~6A methylation modification of CRNDE.