MicroRNA-149 suppresses the malignant phenotypes of ovarian cancer via downregulation of MSI2 and inhibition of PI3K/AKT pathway

L.-W. Zhao, A.-J. Yu, Y.-J. Zhang, X.-C. Wang, B. Han, X.-H. Wang

The First Department of Gynecology, 2The First Department of General Surgery; The Affiliated Hospital of Chengde Medical University, Chengde, China. luwenzhao2009@126.com

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• Oncology

OBJECTIVE: Ovarian cancer (OC) is one of the most lethal gynecologic malignant tumors. Emerging evidence has indicated that the dysregulation of microRNAs (miRNAs/miRs) participates in the OC progression. It has been revealed that miR-149 acts either as an oncogene or a tumour suppressor in various human tumors. The current study focused on the biological roles and potential mechanism of miR-149 in OC.

PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the level of miR-149 expression in 72 pairs of OC tissues and para-cancerous specimens. We further measured the miR-149 levels in OC cells. As we indicated that miR-149 inhibited OC cell viability, we further explored the roles of miR-149 in OC cell invasion and migration by performing the transwell assays. As we suggested that MSI2 was one target for miR-149 in OC cell lines, the expressions and clinical significance of MSI2 in OC were further investigated.

RESULTS: We first detected miR-149 expressions in the OC tissues using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and the data showed that miR-149 was dramatically downregulated in the OC tissue samples in comparison to matched normal tissue samples. Additionally, the downregulation of miR-149 in OC was found to be related to the poor prognosis and malignant clinicopathologic characteristics of patients with OC. MiR-149 overexpression significantly suppressed the OC cell proliferation, invasion, and migration as determined by functional assays, including MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assays and transwell assays. Furthermore, the dual-luciferase reporter assay demonstrated that MSI2 was an efficient target of miR-149 in OC cells. Finally, some findings also revealed that miR-149 exerted its biological function in OC cells via direct regulation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT).

CONCLUSIONS: Collectively, miR-149 exerted anti-OC roles at least partially by regulating MSI2 via PI3K/AKT. The findings of this study suggested that miR-149 might be a promising target in the diagnosis and prognosis for OC patients.

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