Upregulated miRNA-1236-3p in osteosarcoma inhibits cell proliferation and induces apoptosis via targeting KLF8

Y. Sun, L. Cao, J.-T. Lin, Y. Yuan, Z.-L. Cao, J.-D. Jia

Trauma Department of Orthopedics, Yantaishan Hospital, Yantai, China. khqrel@163.com

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• Oncology

OBJECTIVE: To elucidate the regulatory effect of miRNA-1236-3p on the cellular behaviors of osteosarcoma (OS) cells, and to provide novel hallmarks and therapeutic targets for the diagnosis, treatment, and prognosis of OS.

PATIENTS AND METHODS: Relative level of miRNA-1236-3p in OS tissues and cell lines was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Regulatory effects of miRNA-1236-3p on the proliferative ability of HOS and U-2OS cells were evaluated by cell counting kit-8 (CCK-8) assay. Through flow cytometry, the potential influences of miRNA-1236-3p on cell cycle progression and apoptosis of OS cells were examined. Subsequently, the dual-luciferase reporter gene assay was conducted to explore the binding of KLF8 (Krüppel-like factor 8) to miRNA-1236-3p. Regulatory effects of KLF8 on cellular behaviors of OC cells were also evaluated.

RESULTS: MiRNA-1236-3p was downregulated in OS tissues relative to controls. Meanwhile, miRNA-1236-3p was lowly expressed in OS with worse TNM stage or distant metastasis. The overexpression of miRNA-1236-3p in HOS and U-2OS cells suppressed the proliferative ability, arrested the cell cycle in the G0/G1 phase and induced apoptosis. Conversely, miRNA-1236-3p knockdown obtained the opposite trends. KLF8 was verified to bind to miRNA-1236-3p, and its expression was negatively regulated by miRNA-1236-3p in OS cells. A series of functional experiments displayed the oncogenic role of KLF8 in OS.

CONCLUSIONS: MiRNA-1236-3p is downregulated in OS tissues and cell lines. The overexpression of miRNA-1236-3p suppresses the proliferative ability and induces apoptosis of OS cells via downregulating KLF8.

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