MicroRNA‑92b promotes cell proliferation and invasion in osteosarcoma by directly targeting Dickkopf‑related protein 3
- Qing Wu
- Wei Zhou
- Qiong Feng
- Xing Liu
- Yanfei Xiong
- Hui Li
Published online on: October 23, 2017
Copyright: © Wu et al.
This is an open access article distributed under the terms of Creative Commons Attribution License.
Deregulation of microRNA‑92b (miR‑92b) has been implicated in osteosarcoma. However, the underlying regulatory mechanism of miR‑92b in osteosarcoma growth and metastasis remains largely unclear. In the present study, reverse transcription‑quantitative polymerase chain reaction and western blotting were used to measure mRNA and protein expression. MTT and Transwell assays were conducted to determine cell proliferation and invasion, and a luciferase reporter assay was performed to confirm the association between miR‑92b and Dickkopf3‑related protein (DKK3). The results demonstrated that miR‑92b was significantly upregulated in osteosarcoma tissues compared with matched adjacent non‑tumor tissues. Additionally, high miR‑92b levels were significantly associated with lung metastasis and advanced tumor, node, metastasis stage (P<0.05) but not with age, sex, tumor size, location, serum lactate dehydrogenase or serum alkaline phosphatase. miR‑92b expression was also significantly upregulated in osteosarcoma cell lines compared with normal osteoblast cells. Knockdown of miR‑92b significantly inhibited the proliferation and invasion of osteosarcoma U2OS cells (P<0.01). By contrast, overexpression of miR‑92b significantly increased U2OS cell proliferation and invasion (P<0.01). DKK3 was identified as a target gene of miR‑92b and it was demonstrated that DKK3 expression was negatively regulated by miR‑92b in U2OS cells. Restoration of DKK3 expression abrogated the increased proliferation and invasion of U2OS cells induced by miR‑92b overexpression. Notably, DKK3 was significantly downregulated in osteosarcoma tissues compared with adjacent non‑tumor tissues and its expression was inversely correlated to miR‑92b levels in osteosarcoma tissues. Taken together, these data indicate that miR‑92b promotes cell proliferation and invasion in osteosarcoma by targeting DKK3. Therefore, miR‑92b may become a potential therapeutic target for osteosarcoma.