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MiRNA-584 suppresses the progression of ovarian cancer by negatively regulating LPIN1.

Eur Rev Med Pharmacol Sci. 2020 Feb;24(3):1062-1071. doi:10.26355/eurrev_202002_20156
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摘要


OBJECTIVE:The aim of the study was to detect the expression level of microRNA-584 (miRNA-584) in ovarian cancer (OCa) and to elucidate its regulatory effect on OCa progression by regulating LPIN1. PATIENTS AND METHODS:Expression levels of miRNA-584 and LPIN1 in 31 matched OCa tissues and paracancerous tissues were detected. The relationship of miRNA-584 level with clinical indicators and prognosis of OCa patients was analyzed. Influences of miRNA-584/LPIN1 regulatory loop on malignant phenotypes of OVCAR3 and PEO1 cells were assessed. In addition, the interaction between miRNA-584 and LPIN1 was confirmed by Dual-Luciferase reporter gene assay and rescue experiments. RESULTS:MiRNA-584 was lowly expressed in OCa tissues, while LPIN1 was highly expressed. OCa patients expressing a low level of miRNA-584 suffered from higher rates of lymphatic metastasis and distant metastasis, as well as worse survival. The overexpression of miRNA-584 in OVCAR3 cells attenuated proliferative and migratory abilities, while the knockdown of miRNA-584 in PEO1 cells yielded the opposite results. LPIN1 was verified to be the target binding to miRNA-584 and its level was negatively regulated by miRNA-584. The overexpression of LPIN1 accelerated OCa cells to proliferate and migrate. Importantly, LPIN1 was responsible for OCa progression regulated by miRNA-584. CONCLUSIONS:MiRNA-584 is downregulated in OCa tissues and cell lines. MiRNA-584 level is correlated with lymphatic metastasis, distant metastasis, and poor prognosis in OCa patients. By negatively regulating LPIN1, miRNA-584 suppresses the malignant progression of OCa.

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