Abstract
Monocyte chemotactic protein induced protein 3 (MCPIP3) belongs to the Cys–Cys–Cys–His (CCCH)-zinc finger protein family and contains a highly conserved CCCH-zinc finger domain and a Nedd4-BP1 YacP nuclease (NYN) domain. Previous studies showed that MCPIP3 inhibits the expression of proinflammatory genes, such as vascular cell adhesion molecule (VCAM)-1, in human endothelial cells, but the roles and functions of MCPIP3 in cancer cells are still unknown. In human colorectal cancer specimens, we found that the messenger RNA expression of MCPIP3 was significantly downregulated in cancer tissues compared to adjacent normal tissues (18/25; average fold change of 8.18). Two cell models were used to demonstrate the anti-migration activity of MCPIP3. First, Tet-on T-REx-293/HA-MCPIP3 cells were used to examine whether MCPIP3 can change epithelial–mesenchymal transition (EMT)-related gene expressions. Second, we used two human colorectal cancer cell lines, SW620 and HCT116, to prove the role of MCPIP3 in regulating EMT-related gene expressions. We found that overexpression of MCPIP3 inhibited cell migration according to a wound-healing assay and Transwell invasion assay and vimentin expression, and increased E-cadherin expression in these two cell lines. These results suggest that MCPIP3 might play a negative role in cell migration of human colorectal cancer cells.
Highlights
Colorectal cancer (CRC) ranks third among all cancers in mortality
The results revealed that Monocyte chemotactic protein induced protein 3 (MCPIP3) mRNA expression in tumor tissues was lower
Since we have found that overexpression of MCPIP3 for 5 days resulted in significant decrease of cell proliferation (Figure S4)
Summary
Colorectal cancer (CRC) ranks third among all cancers in mortality. It is the third most diagnosed malignant tumor worldwide [1]. FFiigguurree 33AA sshhoowwss tthhaatt eexxpprreessssiioonnss ooff tthhee MMCCPPIIPP33 aanndd EE--ccaaddhheerriinn pprrootteeiinnss iinnccrreeaasseedd wwiitthh aa pprroolloonnggeedd DDooxx ttrreeaattmmeenntt dduurraattiioonn. Overexpression of MCPIP3 Inhibits Cell Migration and Affects EMT-Related Gene Expressions in Human CRC Cells. EEffffeeccttss ooff MMCCPPIIPP33 oovveerreexxpprreessssiioonn oonn tthhee cceellll mmiiggrraattiioonn ooff hhuummaann HHCCTT111166 aanndd SSWW662200 ccoolloorreeccttaall ccaanncceerrcceelllsls. HHCCTT111166 aanndd SSWW662200 cceellllss wweerree ttrraannssdduucceedd wwiitthh aa lleennttiivviirraall vveeccttoorr ((aatt aann MMOOII ooff 33)) eexxpprreessssiinngg tthhee iinnddiiccaatteedd eennhhaanncceeddggrreeeenn fflflluuoorreesscceenntt pprrootteeiinn ((EEGGFFPP)),, HHAA--MMCCPPIIPP33,, aannddHHAA--MMCCPPIIPP33--DD225511NN mmuuttaanntt aanndd tthhheeennnccucuultlluttuurerrededdfoffroor2r422h44. The present study found that overexpression of MCPIP3 inhibited MMP-2 mRNA expression (Figure 3B), indicating that MCPIP3 may inhibit MMP gene expression and tumor cell metastasis. High expression of VCAM-1 reduces E-cadherin expression and elevates vimentin expression, thereby enhancing cell adhesion, migration, and invasion Both a previous study [20] and the current study identified that overexpression of MCPIP3 can effectively inhibit VCAM-1 expression (Figure 3). A great number of macrophages may have existed in some of tumor tissues, and MCPIP3 expression may have been influenced by these macrophages
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