2. Academic Validation
  3. Liver cancer cell-secreted exosomes promote bone metastasis of liver cancer by facilitating osteoclast differentiation through the miR-574-5p/BMP2 axis

Liver cancer cell-secreted exosomes promote bone metastasis of liver cancer by facilitating osteoclast differentiation through the miR-574-5p/BMP2 axis

  • Pathol Res Pract. 2023 Apr 25;245:154485. doi: 10.1016/j.prp.2023.154485.
Tengfei Li 1,  Miaomiao Li 2,  Ye Peng 1,  Xiaojie Li 1,  Yufei Chen 1,  Jinkang Zhang 1,  Zhenyu Zhang 1,  Hongxing Zhang 1,  Junjie Du 3
Affiliations

Affiliations

  • 1 Department of Orthopedics, Air Force Medical Center of PLA, Beijing, China.
  • 2 The 9th Clinical College, PKU, Beijing, China; Department of Interventional Therapy, Beijing Shijitan Hospital, Capital Medical University, PKU, Beijing, China.
  • 3 Department of Orthopedics, Air Force Medical Center of PLA, Beijing, China; Graduate School of China Medical University, Shenyang, Liaoning Province, China. Electronic address: [email protected].
PMID: 37120909 DOI: 10.1016/j.prp.2023.154485
Abstract

Bone metastasis of liver Cancer leads to a worse prognosis with no appropriate treatment clinically. Exosomes are associated with tumor bone metastasis. This study aimed to investigate the effects of liver Cancer cell-derived exosomes on bone metastasis. Exosomes were isolated from Hep3B cells, and the effects of osteoclast differentiation were assessed using TRAP assay. The expression of OPG and RANKL was assessed using qRT-PCR. The interaction of miR-574-5p and BMP2 was analyzed using luciferase reporter analysis, RNA pull-down, and qRT-PCR. We found that Hep3B cells promoted osteoclast differentiation of RANKL-induced Raw264.7 cells by secreting exosomes, with decreased OPG and increased RANKL expression. The exosomes were isolated from Hep3B cells, which promoted osteoclast differentiation. Exosomal miR-574-5p promoted osteoclastogenesis by targeting BMP2. Moreover, exosomes facilitated osteoclast differentiation, promoting bone metastasis by regulating miR-574-3p in vivo. In conclusion, liver Cancer cell-derived exosomal miR-574-5p promoted osteoclastogenesis by regulating BMP2, thereby promoting bone metastasis in vivo. The findings suggest that liver Cancer cell-released exosomes are the potential therapeutic approach for bone metastatic liver Cancer. DATA AVAILABILITY STATEMENT: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Keywords

Bone metastasis; Exosome; Liver cancer; MiR-574–5p/BMP2 axis; Osteoclast differentiation.

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