MicroRNA-302 inhibits cell migration and invasion in cervical cancer by targeting DCUN1D1.

Abstract

MicroRNA serve crucial roles in a variety of human cancer types. The miR-302-367 cluster has been reported to suppress the proliferation of cervical carcinoma cells through the novel target AKT1; however, the molecular mechanism of miR-302 in cervical cancer metastasis remains unclear. The present study aimed to investigate the clinical significance of miR-302-3p expression in cervical cancer, and to examine the regulatory mechanism of miR-302-3p in the malignant phenotypes of cervical cancer cells. The present data indicated that miR-302-3p was significantly downregulated in cervical cancer tissues compared with the level in adjacent non-tumor tissues, and low expression of miR-302-3p was significantly associated with node metastasis, advanced clinical stage, and poor prognosis in patients with cervical cancer. Restoration of miR-302-3p expression caused a significant reduction in cervical cancer cell migration and invasion. Defective in cullin neddylation 1 domain containing 1 (DCUN1D1) was identified as a novel target gene of miR-302-3p, and miR-302-3p negatively regulated the mRNA and protein expression of DCUN1D1 in cervical cancer HeLa cells. Additionally, overexpression of DCUN1D1 rescued the effects of miR-302-3p on the migration and invasion of cervical cancer cells. Furthermore, DCUN1D1 was upregulated in cervical cancer tissues compared with the levels in adjacent tissues, and its high expression was associated with node metastasis, advanced clinical stage, and shorter survival time in patients with cervical cancer. Notably, a negative correlation between miR-302-3p and DCUN1D1 expression in cervical cancer tissues was observed. Taken together, the present study suggests that miR-302-3p serves a suppressive role in cervical cancer metastasis, partly at least, via directly targeting DCUN1D1. Therefore, miR-302-3p/DCUN1D1 may be a potential therapeutic target for cervical cancer treatment.