Abstract: To investigate whether lncRNA MALAT1 affects the migration and proliferation of breast cancer cells through the regulation with histone methyltransferase SMYD3, the endogenous MALAT1 in the MCF-7 and MDA-MB-231 breast cancer cells were knocked down by siRNA, and then the migration and proliferation of cells were detected by wound healing migration and MTT assay. The effects of si-MALAT1 on the mRNA and protein levels of miRNA-124, SMYD3 and its downstream genes were detected by Real time PCR and Western blot. The results showed that siRNA-targeted knockdown of MALAT1 reduced the migration and proliferation of breast cancer cells, and inhibited the transcriptional expression of SMYD3 and its downstream genes, including N-cadherin, MYL9, MMP9 and CYR61, and up-regulated miR-124. Overexpression of miR-124 reduced the expression of SMYD3 in breast cancer cells, and knockdown of MALAT1 attenuated the promotion of SMYD3 protein expression by miR-124 inhibitors. In addition, SMYD3 overexpression activated MALAT1 transcription, whereas siRNA interference with SMYD3 downregulated MALAT1. These results indicate that LncRNA MALAT1 acted as a competing endogenous RNA(ceRNA)of miR-124 to regulate expression of SMYD3 in breast cancer cells, and SMYD3 can activate the transcription of MALAT1, which will affect the proliferation and migration of breast cancer cells.