Title : 1 CircMETTL 3 , upregulated in a m 6 A-dependent manner , promotes 2 breast cancer progression

23 Growing evidence indicates N6-methyladenosine (m6A) has biological 24 function in oncogenesis. METTL3, the catalytic component, is the most 25 important part of methyltransferase complex and plays a crucial role in cancers. 26 However, the biological function of circRNAs derived from METTL3 in breast 27 cancer and the underlying molecular mechanism remains unclear. Herein, we 28 report circMETTL3, which has not been explored in breast cancer, and it is 29 markedly upregulated in breast cancer. Moreover, we uncovered that 30 circMETTL3 could facilitate cell proliferation, migration and invasion in breast 31 cancer. Mechanism investigation showed that circMETTL3 might act as a 32 competing endogenous RNA (ceRNA) of miR-31-5p and upregulate its target 33 cyclin-dependent kinases (CDK1). Moreover, m6A modification of 34 circMETTL3 might affect its expression. Taken together, our results elucidate 35 that circMETTL3 promotes breast cancer progression through 36 circMETTL3/miR-31-5p/CDK1 axis. Moreover, METTL3, the host gene of 37 circMETTL3, may regulate circMETTL3 expression in a m6A-dependent 38 manner, while circMETTL3 has no effect on METTL3 expression, providing a 39 new relationship between the circRNA and the corresponding host gene. Thus, 40 it may serve as a new therapeutic target for breast cancer. 41