Abstract: Objective To investigate the functions of Monocyte chemotactic protein-induced protein 1 (MCPIP1) in human breast cancer cell line MDA-MB-231. Methods MDA-MB-231 cells were transfected with GFP-tagged MCPIP1 by Tet-on inducing expression system. Endogenous MCPIP1 was knocked down by stable expressing shRNA. MTT assay was performed to measure the growth of MDA-MB-231 cells after overexpression or knockdown of MCPIP1. FACS method was used to analysis cell cycle in MDA-MB-231 cells. Real-time PCR was used to test the expression of cell cycle-related mRNAs expression and their half-lives. RNA-IP experiment was conducted to detect the mRNA directly enriched by MCPIP1. Luciferase assay was performed to determine whether the mRNA decay was mediated through 3’UTR. Results MCPIP1 overexpression inhibited cell proliferation significantly (P<0.05), while knockdown MCPIP1 promoted cell proliferationwith statistical significances (P<0.05). MCPIP1 induced cell cycle arrest in MDA-MB-231 with statistical significance (P<0.01). MCPIP1 overexpression reduced the half-lives of cell cycle mRNAs (CDK2，CDK6，Cyclin D1，Cyclin E1，respectively) with significance (P<0.01). In addition, cell cycle-related mRNAs were able to be pulled down by GFP-MCPIP1but not isotype IgG (P< 0.05). Compared with control vector, MCPIP1 significant suppressed luciferase activitiesof all four 3’UTR reporters (P< 0.05). Conclusion MCPIP1 functions as a tumor suppressor in human breast cancer cell line MDA-MB-231 through inducing G1 cell cycle arrest.

Key words: breast cancer, MCPIP1, MDA-MB-231, cell cycle