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

Y.-M. Zhu, P. Chen, L. Shi, T. Zhu, X. Chen

Department of Gynecological Oncology, Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China. xiang10301030@163.com

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• Oncology

OBJECTIVE: 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.

PATIENTS AND METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

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