MicroRNA-203-mediated posttranscriptional deregulation of CPEB4 contributes to colorectal cancer progression

• CPEB4 is aberrantly expressed in human colorectal cancers.
• Knockdown of CPEB4 inhibited colorectal cancer cell proliferation and enhanced apoptosis.
• CPEB4 is a direct target of miR-203 and inversely correlates with miR-203 expression.
• miR-203 inhibited cell growth and enhanced cell apoptosis in CPEB4 dependent manner.
• miR-203 is an upstream regulator of the CPEB4-induced apoptosis pathway.

Elevated cytoplasmic polyadenylation element-binding 4 (CPEB4) is aberrantly expressed in several malignant cancers. However, its expression pattern, clinical significance, and biological function in colorectal cancer are still unknown. In this study, we demonstrated that CPEB4 is abundantly overexpressed in colorectal cancers and has the potential to be used for predicting clinical outcomes of colorectal cancer patients. We suppressed CPEB4 expression by small interfering RNA (siRNA) in SW480 and LOVO cells to clarify the role of CPEB4 on the cell apoptosis and proliferation in vitro. Further study revealed that knockdown of CPEB4 decreased the expression of anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL), but enhanced the expression of B-cell lymphoma-2-associated X (Bax). In addition, we indicated that CPEB4 is a novel target of miR-203, a tumor suppressive microRNA. Notably, restoration of CPEB4 in SW480 cells inhibited miR-203-induced apoptosis signaling pathway, which in turn enhanced cell proliferation and suppressed cell apoptosis. Taken together, our findings imply that posttranscriptional deregulation of CPEB4 contributes to the inhibited cell proliferation and the enhanced cell apoptosis in colorectal cancer, and directly targeting CPEB4 by miR-203 might be a novel strategy in colorectal cancer treatment.