MiR-4429 suppresses the malignant development of ovarian cancer by targeting YOD1.

Abstract

The purpose of this study was to assess the clinical significance of microRNA-4429 (miR-4429) in the development and prognosis of ovarian cancer, and to explore the regulatory role of miR-4429 in migratory potential of ovarian cancer cells. MiR-4429 levels in paired ovarian cancer species and paracancerous ones were examined. Then, the relationship between miR-4429 level and clinical features of ovarian cancer patients was analyzed. Potential influences of miR-4429 on migratory potentials in CAOV3 and SKOV3 cells were explored by transwell assay. After that, the interaction between miR-4429 and its downstream gene YOD1, and their involvement in the malignant development of ovarian cancer were finally demonstrated through Luciferase assay and rescue experiments. The results revealed that miR-4429 was downregulated in ovarian cancer tissues and cell lines. Its level was significantly correlated with rates of lymphatic metastasis (p=0.018) and distant metastasis (p=0.012) but not with age, tumor size, and tumor stage in ovarian cancer patients. Survival analysis uncovered that a low level of miR-4429 was unfavorable to PFS and OS in ovarian cancer patients. Besides, the overexpression of miR-4429 inhibited migratory potential in CAOV3 cells, and conversely, the knockdown of miR-4429 in SKOV3 cells obtained the opposite result. Moreover, YOD1 was proved to be the downstream gene binding to miR-4429. It was highly expressed in ovarian cancer tissues and negatively regulated by miR-4429. Rescue experiments finally identified that YOD1 was responsible for migratory potential changes in ovarian cancer cells regulated by miR-4429. MiR-4429 is downregulated in ovarian cancer tissues, and its level is closely linked to metastasis and prognosis in ovarian cancer patients. By negatively regulating YOD1 level, miR-4429 suppresses the malignant development of ovarian cancer.