PMID- 35600978
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2452-199X (Electronic)
IS  - 2452-199X (Linking)
VI  - 19
DP  - 2023 Jan
TI  - Zinc oxide nanoparticles inhibit osteosarcoma metastasis by downregulating 
      beta-catenin via HIF-1alpha/BNIP3/LC3B-mediated mitophagy pathway.
PG  - 690-702
LID - 10.1016/j.bioactmat.2022.05.006 [doi]
AB  - 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 Zn(2+) released from ZnO NPs induced 
      downregulation of beta-catenin expression via HIF-1alpha/BNIP3/LC3B-mediated mitophagy 
      pathway. ZnO NPs combined with ICG-001, a beta-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 
      beta-catenin expression which indicated the role of beta-catenin in OS development. In 
      summary, our current study not only proved that ZnO NPs can inhibit OS metastasis 
      by degrading beta-catenin in HIF-1alpha/BNIP3/LC3B-mediated mitophagy pathway, but also 
      provided a far-reaching potential of ZnO NPs in clinical OS treatment with 
      metastasis.
CI  - (c) 2022 The Authors.
FAU - He, Guanping
AU  - He G
AD  - Department of Orthopedics, Beijing Chao-Yang Hospital, Capital Medical 
      University, Beijing, 100020, China.
AD  - Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, 
      China.
FAU - Nie, Jing-Jun
AU  - Nie JJ
AD  - Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical 
      Materials, Beijing Research Institute of Traumatology and Orthopaedics, Beijing 
      Jishuitan Hospital, Beijing, 100035, China.
FAU - Liu, Xiao
AU  - Liu X
AD  - Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, 
      China.
FAU - Ding, Zihao
AU  - Ding Z
AD  - Department of Orthopedics, Beijing Chao-Yang Hospital, Capital Medical 
      University, Beijing, 100020, China.
FAU - Luo, Peng
AU  - Luo P
AD  - Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical 
      Materials, Beijing Research Institute of Traumatology and Orthopaedics, Beijing 
      Jishuitan Hospital, Beijing, 100035, China.
FAU - Liu, Yu
AU  - Liu Y
AD  - Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, 
      China.
FAU - Zhang, Bo-Wen
AU  - Zhang BW
AD  - Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical 
      Materials, Beijing Research Institute of Traumatology and Orthopaedics, Beijing 
      Jishuitan Hospital, Beijing, 100035, China.
FAU - Wang, Renxian
AU  - Wang R
AD  - Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical 
      Materials, Beijing Research Institute of Traumatology and Orthopaedics, Beijing 
      Jishuitan Hospital, Beijing, 100035, China.
FAU - Liu, Xiaoguang
AU  - Liu X
AD  - Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, 
      China.
FAU - Hai, Yong
AU  - Hai Y
AD  - Department of Orthopedics, Beijing Chao-Yang Hospital, Capital Medical 
      University, Beijing, 100020, China.
FAU - Chen, Da-Fu
AU  - Chen DF
AD  - Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical 
      Materials, Beijing Research Institute of Traumatology and Orthopaedics, Beijing 
      Jishuitan Hospital, Beijing, 100035, China.
LA  - eng
PT  - Journal Article
DEP - 20220513
PL  - China
TA  - Bioact Mater
JT  - Bioactive materials
JID - 101685294
PMC - PMC9112061
OTO - NOTNLM
OT  - HIF-1alpha/BNIP3/LC3B-mediated mitophagy pathway
OT  - Metastasis
OT  - Osteosarcoma
OT  - Zinc oxide nanoparticle
COIS- The authors declare no conflict of interest.
EDAT- 2022/05/24 06:00
MHDA- 2022/05/24 06:01
PMCR- 2022/05/13
CRDT- 2022/05/23 04:01
PHST- 2022/03/29 00:00 [received]
PHST- 2022/05/04 00:00 [revised]
PHST- 2022/05/04 00:00 [accepted]
PHST- 2022/05/23 04:01 [entrez]
PHST- 2022/05/24 06:00 [pubmed]
PHST- 2022/05/24 06:01 [medline]
PHST- 2022/05/13 00:00 [pmc-release]
AID - S2452-199X(22)00217-1 [pii]
AID - 10.1016/j.bioactmat.2022.05.006 [doi]
PST - epublish
SO  - Bioact Mater. 2022 May 13;19:690-702. doi: 10.1016/j.bioactmat.2022.05.006. 
      eCollection 2023 Jan.