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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Exosomal CircRNA_102619–miR-330-3p Interaction Regulates Osteosarcoma Progression and Metastasis by Forming the Lung Pre-Metastatic Niche

  • Ming-Yu Lien1,2
  • Yu-Hsiang Chang3
  • Hsiao-Chi Tsai4
  • Chin-Jung Hsu5,6
  • Chun-Lin Liu7
  • Jeng-Hung Guo7
  • Tsung-Yu Ho5
  • Liang-Wei Lin8
  • Yi-Chin Fong5,9,10
  • Chih-Hsin Tang1,3,8,11,12
12 affiliations
  1. 1School of Medicine, China Medical University, Taichung 40402, Taiwan
  2. 2Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung 40447, Taiwan
  3. 3Program for Cancer Biology and Drug Discovery, China Medical University, Taichung 40402, Taiwan
  4. 4Department of Medicine Research, China Medical University Beigang Hospital, Yunlin 65152, Taiwan
  5. 5Department of Orthopedic Surgery, China Medical University Hospital, Taichung 40447, Taiwan
  6. 6School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
  7. 7Department of Neurosurgery, China Medical University Hospital, Taichung 40447, Taiwan
  8. 8Department of Pharmacology, School of Medicine, China Medical University, Taichung 40402, Taiwan
  9. 9Department of Sports Medicine, College of Health Care, China Medical University, Taichung 40402, Taiwan
  10. 10Department of Orthopedic Surgery, China Medical University Beigang Hospital, Yunlin 65152, Taiwan
  11. 11Chinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan
  12. 12Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung 41354, Taiwan
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Abstract

Osteosarcoma, the most prevalent primary bone tumor, predominantly influences children and adolescents. The pre-metastatic niche (PMN) is a specialized microenvironment that forms before clinically detectable metastatic lesions. Cancer-associated fibroblasts (CAFs) play a crucial function in triggering lung metastasis by coordinating PMN formation in the lung. We found that circRNA_102619, delivered by osteosarcoma-derived extracellular vesicles (EVs), promotes the reprogramming of lung fibroblasts (LFs) into CAFs and PMN formation both in vitro and in vivo. High-throughput protein array analysis revealed that CXCL10, a critical factor secreted by CAFs, drives osteosarcoma proliferation, migration, and resistance to natural killer (NK) cell cytotoxicity. Additionally, circRNA_102619 acts as a sponge for miR-330-3p, thereby controlling CXCL10 production. Importantly, in vivo studies confirmed that osteosarcoma-derived EVs enhance lung PMN formation, promoting osteosarcoma progression and metastasis. Inhibiting osteosarcoma-derived EVs represents a novel strategy to block osteosarcoma progression and metastasis.

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Cite

BibTeXRIS
BibTeX
@article{lien2026exosomal,
  title = {{Exosomal CircRNA_102619–miR-330-3p Interaction Regulates Osteosarcoma Progression and Metastasis by Forming the Lung Pre-Metastatic Niche}},
  author = {Ming-Yu Lien and Yu-Hsiang Chang and Hsiao-Chi Tsai and Chin-Jung Hsu and Chun-Lin Liu and Jeng-Hung Guo and Tsung-Yu Ho and Liang-Wei Lin and Yi-Chin Fong and Chih-Hsin Tang},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27209193},
  url = {https://www.mdpi.com/1422-0067/27/20/9193},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Exosomal CircRNA_102619–miR-330-3p Interaction Regulates Osteosarcoma Progression and Metastasis by Forming the Lung Pre-Metastatic Niche
AU  - Ming-Yu Lien
AU  - Yu-Hsiang Chang
AU  - Hsiao-Chi Tsai
AU  - Chin-Jung Hsu
AU  - Chun-Lin Liu
AU  - Jeng-Hung Guo
AU  - Tsung-Yu Ho
AU  - Liang-Wei Lin
AU  - Yi-Chin Fong
AU  - Chih-Hsin Tang
PY  - 2026
DA  - 2026/10/01
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27209193
UR  - https://www.mdpi.com/1422-0067/27/20/9193
AB  - Osteosarcoma, the most prevalent primary bone tumor, predominantly influences children and adolescents. The pre-metastatic niche (PMN) is a specialized microenvironment that forms before clinically detectable metastatic lesions. Cancer-associated fibroblasts (CAFs) play a crucial function in triggering lung metastasis by coordinating PMN formation in the lung. We found that circRNA_102619, delivered by osteosarcoma-derived extracellular vesicles (EVs), promotes the reprogramming of lung fibroblasts (LFs) into CAFs and PMN formation both in vitro and in vivo. High-throughput protein array analysis revealed that CXCL10, a critical factor secreted by CAFs, drives osteosarcoma proliferation, migration, and resistance to natural killer (NK) cell cytotoxicity. Additionally, circRNA_102619 acts as a sponge for miR-330-3p, thereby controlling CXCL10 production. Importantly, in vivo studies confirmed that osteosarcoma-derived EVs enhance lung PMN formation, promoting osteosarcoma progression and metastasis. Inhibiting osteosarcoma-derived EVs represents a novel strategy to block osteosarcoma progression and metastasis.
SN  - 1422-0067
ER  -