Zinc oxide nanoparticles inhibit osteosarcoma metastasis by downregulating β-catenin via HIF-1α/BNIP3/LC3B-mediated mitophagy pathway.
Zinc oxide nanoparticles inhibit osteosarcoma metastasis by downregulating β-catenin via HIF-1α/BNIP3/LC3B-mediated mitophagy pathway.
复制标题
氧化锌纳米颗粒通过 HIF-1α/BNIP3/LC3B 介导的线粒体自噬途径下调 β-catenin 抑制骨肉瘤转移
DOI：
10.1016/j.bioactmat.2022.05.006
复制
发表时间：
2023-01
影响因子：
18.9
通讯作者：
Chen, Da-Fu
中科院分区：
文献类型：
--
作者：
He, Guanping;Nie, Jing-Jun;Liu, Xiao;Ding, Zihao;Luo, Peng;Liu, Yu;Zhang, Bo-Wen;Wang, Renxian;Liu, Xiaoguang;Hai, Yong;Chen, Da-Fu
骨肉瘤的治疗面临着许多挑战，尤其是一旦发生转移，生存率很低。因此，探索有效抑制OS转移的新的OS治疗策略至关重要。生物活性纳米颗粒如氧化锌纳米颗粒（ZnO NPs）能有效抑制OS的生长，但其对肿瘤转移的影响及其机制尚不清楚。本研究首先制备了分散性良好的ZnO纳米颗粒，并证明ZnO纳米颗粒可以抑制OS转移相关的恶性行为，包括迁移、侵袭和上皮-间质转化（EMT）。RNA-Seqs分析发现，ZnO NP处理的OS细胞中差异表达基因（DEG）在Wnt和HIF-1信号通路中富集。我们进一步证明了Zn 2+通过HIF-1α/BNIP 3/LC 3B介导的线粒体自噬途径诱导β-catenin表达下调。ZnO纳米粒联合β-catenin抑制剂ICG-001对OS肺转移有协同抑制作用，并延长生存期。此外，组织微阵列（TMA）检测到β-catenin在OS患者中的高表达，提示β-catenin在OS发生发展中的作用。综上所述，我们的研究不仅证明了ZnO纳米颗粒可以通过降解HIF-1α/BNIP 3/LC 3B介导的线粒体自噬通路中的β-catenin抑制OS转移，而且为ZnO纳米颗粒在临床治疗OS转移提供了深远的潜力。生物活性ZnO NP通过HIF-1α/BNIP 3/LC 3B介导的线粒体自噬途径诱导β-catenin表达下调，有效抑制OS转移。从生物活性ZnO NPs释放的Zn 2+触发OS转移抑制。ZnO纳米颗粒通过HIF-1α/BNIP 3/LC 3B介导的线粒体自噬途径降低β-catenin的表达抑制OS转移。组织芯片检测到OS患者中β-catenin的高表达，证实了ZnO纳米颗粒在临床上的潜力。
Osteosarcoma (OS) therapy faces many challenges, especially the poor survival rate once metastasis occurs. Therefore, it is crucial to explore new OS treatment strategies that can efficiently inhibit OS metastasis. Bioactive nanoparticles such as zinc oxide nanoparticles (ZnO NPs) can efficiently inhibit OS growth, however, the effect and mechanisms of them on tumor metastasis are still not clear. In this study, we firstly prepared well-dispersed ZnO NPs and proved that ZnO NPs can inhibit OS metastasis-related malignant behaviors including migration, invasion, and epithelial-mesenchymal transition (EMT). RNA-Seqs found that differentially expressed genes (DEGs) in ZnO NP-treated OS cells were enriched in wingless/integrated (Wnt) and hypoxia-inducible factor-1 (HIF-1) signaling pathway. We further proved that Zn2+ released from ZnO NPs induced downregulation of β-catenin expression via HIF-1α/BNIP3/LC3B-mediated mitophagy pathway. ZnO NPs combined with ICG-001, a β-catenin inhibitor, showed a synergistic inhibitory effect on OS lung metastasis and a longer survival time. In addition, tissue microarray (TMA) of OS patients also detected much higher β-catenin expression which indicated the role of β-catenin in OS development. In summary, our current study not only proved that ZnO NPs can inhibit OS metastasis by degrading β-catenin in HIF-1α/BNIP3/LC3B-mediated mitophagy pathway, but also provided a far-reaching potential of ZnO NPs in clinical OS treatment with metastasis. Bioactive ZnO NP-induced downregulation of β-catenin expression via HIF-1α/BNIP3/LC3B-mediated mitophagy pathway efficiently triggers OS metastasis inhibition. Zn2+ released from bioactive ZnO NPs trigger OS metastasis inhibition. ZnO NPs inhibit OS metastasis through degrading β-catenin expression via HIF-1α/BNIP3/LC3B-mediated mitophagy pathway. Tissue microarray of OS patients detected higher β-catenin expression which confirmed the potential of ZnO NPs in clinical.
登录
查看更多内容
影响因子：
6.6
作者：
Rasmussen JW;Martinez E;Louka P;Wingett DG
通讯作者：
Wingett DG
影响因子：
4
作者：
Cai, Yu;Cai, Tiange;Chen, Yan
通讯作者：
Chen, Yan
影响因子：
7.5
作者：
Mazure, Nathalie M.;Pouyssegur, Jacques
通讯作者：
Pouyssegur, Jacques
影响因子：
2.7
作者：
Peng, Yin-xiao;Yu, Bin;Quan, Zheng-xue
通讯作者：
Quan, Zheng-xue
影响因子：
1.9
作者：
Okinaka, Y;Takahashi, M
通讯作者：
Takahashi, M