PDZRN4-mediated colon cancer cell proliferation and dissemination is regulated by miR-221-3p

BACKGROUND: Suppression of PDZRN4 expression in colon cancer tissues may be associated with elevated levels of the microRNA 221 (miR-211). To uncover potential targets for treatment, the present study investigated PDZRN4 in colon cancer development, and explored the role of miR-221-3p in the regulation of PDZRN4. METHODS: RNA expression arrays were searched in the NCBI database, and PDZRN4 (PDZ domain containing ring finger 4) was selected as a potential downregulated gene in colon cancer. PDZRN4 mRNA and protein in colon cancer and matched normal tissues were analyzed. The proliferation and dissemination of HCT116 cells overexpressing PDZRN4 was assessed via functional assays. Bioinformatics analysis and luciferase reporter assay were applied to determine the regulatory link between miR-221-3p and PDZRN4 mRNA. RESULTS: There was significantly less PDZRN4 mRNA and PDZRN4 protein in colon cancer tissue compared with normal tissues. HCT116 cells overexpressing PDZRN4 were less able to disseminate relative to the control. Expression of PDZRN4 was directly inhibited by miR-221-3p. Knockout of miR-211-3p was associated with attenuated proliferation and dissemination of HCT116 cells. CONCLUSIONS: PDZRN4 may function as a tumor suppressor and is downregulated in colon cancer tissues, possibly due to dysregulation via miR-221-3p. This study provides new insight into colon cancer development.