Purpose: To investigate the potential role of curcumin in osteosarcoma (OS) cell migration and invasion, and also to explore the underlying mechanism of action.
Methods: OS cell lines, Saos-2 and U2OS, were treated with various concentrations of curcumin (0, 10, 20, 50 μM) for 48 h. Transwell assay was used to determine the migratory and invasive activities of human OS cells while miR-33b-5p expression levels were measured using quantitative real time polymerase chain reaction (qRT-PCR). Expressions of metastasis-related genes, such as matrix metalloproteinases (MMPs), were quantified by qRT-PCR or western blot. The interaction between miR33b-5p and Sirtuin 6 (SIRT6) was evaluated by luciferase assay.
Results: Curcumin inhibited the migratory and invasive activities of huamn OS cells, and downregulated MMP2 and MMP9 (p < 0.05). Moreover, in curcumin-treated OS cells, miR-33b-5p expression was upregulated while SIRT6 expression was significantly downregulated (p < 0.05). Overexpression of miR-33b-5p downregulated SIRT6 mRNA and protein expression, whereas transfection with miR-33b-5p inhibitor upregulated SIRT6 expression in OS cells (p < 0.05). Furthermore, curcumin suppressed SIRT6 expression by upregulating miR-33b-5p expression in OS cells. Finally, overexpression of SIRT6 or miR-33b-5p inhibitor reversed the suppression of OS cell metastasis induced by curcumin (p < 0.05).
Conclusion: Curcumin inhibits SIRT6 expression via upregulating miR-33b-5p expression, which leads to the inhibition of OS cell migration and invasion. Thus, curcumin is a potential therapeutic agent for the management of OS.
Mao Shitao,Yu Na,Wang Wei,Mao Yikai,Du Ying,Zhao Qihe,Gu Xiu,Kang Jian
Idiopathic pulmonary fibrosis (IPF), characterized by fibroblast activation and collagen deposition, is a progressive lung disease that lacks effective interventions. Ubiquitin-specific peptidase 10 (USP10) acts as a multifunctional player in inflammatory response and progression of cancers, the effect on pulmonary fibrosis is unknown. Here, we demonstrated downregulated expression of USP10 in fibrotic lung tissues of IPF patients. In the current study, lung tissues were collected at the end of weeks 1, 2, or 3 post bleomycin (BLM)-intratracheal delivery. Consistently, USP10 expression levels were reduced after BLM challenge in a time-dependent manner. Mice treated with lentivirus overexpressing USP10 exhibited mitigative lung injury and reduced collagen deposition. USP10 overexpression enhanced autophagy in BLM-treated mouse lungs. Interestingly, the protective effect of USP10 was attenuated as the pulmonary autophagy flux was blocked by autophagy inhibitor 3-methyladenine (3-MA). Primary human and mouse lung fibroblasts were treated with pro-fibrotic TGF-β1 to verify the role of USP10 in vitro. Mechanically, the deubiquitinating enzyme USP10 interacted with Sirtuin 6 (Sirt6) and inhibited its degradation. Furthermore, USP10 overexpression inhibited the activation of Sirt6-mediated AKT/mTOR pathway in both lung tissues and fibroblasts. Our findings suggest that USP10 might attenuate pulmonary fibrosis through the promotion of Sirt6/AKT/mTOR-mediated autophagy. These data prioritize USP10 as a therapeutic target for treating IPF. Graphical
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