Piperlongumine inhibits the progression of osteosarcoma by downregulating the SOCS3/JAK2/STAT3 pathway via miR-30d-5p

Aims: The present study evaluated the functions of Piperlongumine (PL) in osteosarcoma (OS) cell growth and metastasis both in vitro and in vivo. Main methods: MTT assay was conducted to test the cytotoxic effects of PL on the human osteoblasts line HFOB1.19 and the human normal chondrocyte line C28/I2T. FITC-Annexin V and propidium iodide (PI) were used to examine cell apoptosis. The migration, invasion and relative epithelial-mesenchymal transition were examined by Transwell assay and Western blotting. Reverse transcription-quantitative PCR (RT-qPCR) was performed to analyze the cytokine signaling 3 (SOCS3) mRNA expression. TargetScan database was used to predict the target of SOCS3. The binding association between miR-30d-5p and SOCS3 in U2OS and MG63 cells was evaluated by the dual-luciferase reporter assay. A xenograft model was constructed to evaluate the effect of PL on OS cell growth in vivo. Key findings: The results revealed that PL inhibited the growth, migration, invasion, epithelial-mesenchymal transition, and promoted the apoptosis of OS cells dose-dependently. In addition, PL upregulated the protein levels of suppressor of SOCS3, while it inactivated the JAK2/STAT3 pathway, which was accompanied by a decreased level of microRNA (miR)-30d-5p. Furthermore, SOCS3was confirmed as a novel target of miR-30d-5p. Overexpression of miR-30d-5p not only led to decreased expression of SOCS3, but also dampened the antitumor effect of PL on OS. Significance: The present data demonstrated that PL inhibited the progression of OS via downregulation of the SOCS3-mediated JAK2/STAT3 pathway by inhibiting miR-30d-5p.

Automated summary

The study demonstrated that Piperlongumine (PL) effectively inhibits the growth, migration, invasion, and promotes apoptosis of osteosarcoma cells by downregulating the SOCS3-mediated JAK2/STAT3 pathway.