How are MCPIP1 and cytokines mutually regulated in cancer-related immunity?

Cytokines are secreted by various cell types and act as critical mediators in many physiological processes, including immune response and tumor progression. Cytokines production is precisely and timely regulated by multiple mechanisms at different levels, ranging from transcriptional to post-transcriptional and posttranslational processes. Monocyte chemoattractant protein-1 induced protein 1 (MCPIP1), a potent immunosuppressive protein, was first described as a transcription factor in monocytes treated with monocyte chemoattractant protein-1 (MCP-1) and subsequently found to possess intrinsic RNase and deubiquitinase activities. MCPIP1 tightly regulates cytokines expression via various functions. Furthermore, cytokines such as interleukin 1 beta (IL-1B) and MCP-1 and inflammatory cytokines inducer lipopolysaccharide (LPS) strongly induce MCPIP1 expression. Mutually regulated MCPIP1 and cytokines form a complicated network in the tumor environment. In this review, we summarize how MCPIP1 and cytokines reciprocally interact and elucidate the effect of the network formed by these components in cancer-related immunity with aim of exploring potential clinical benefits of their mutual regulation.

MCPIP1 induces cell cycle arrest in breast cancer cell line MDA-MB-231 / 基础医学与临床

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 analyze 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 significantly inhibited cell proliferation(P<0.05), while knockdown MCPIP1 promoted cell proliferation with 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-MCPIP1 but not isotype IgG(P<0.05).Compared with control vector, MCPIP1 significant suppressed luciferase activities of all four 3′UTR reporters (P<0.05).Conclusions MCPIP1 functions as a tumor suppressor in human breast cancer cell line MDA-MB-231 through inducing G1 cell cycle arrest.