2. Academic Validation
  3. Tumor-derived exosomal lncRNA-MIR193BHG promotes bone metastasis of breast cancer by targeting the miR-489-3p/DNMT3A signaling axis in osteoclasts

Tumor-derived exosomal lncRNA-MIR193BHG promotes bone metastasis of breast cancer by targeting the miR-489-3p/DNMT3A signaling axis in osteoclasts

  • J Transl Med. 2025 Jan 31;23(1):142. doi: 10.1186/s12967-025-06156-4.
Xiaoya Liu # 1 2,  Rui Ma # 3,  Feng Wei # 1,  Maihuan Wang 3,  Yiwei Jiang 1 2,  Peng Zheng 4,  Zhen Cao 5 6 7 8
Affiliations

Affiliations

  • 1 Department of General Surgery, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, 100048, China.
  • 2 Department of General Surgery, School of Medicine, South China University of Technology, Guangzhou, 510006, China.
  • 3 Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China.
  • 4 Department of General Surgery, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, 100048, China. zhengp0228@163.com.
  • 5 Department of General Surgery, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, 100048, China. zhenyacy@163.com.
  • 6 Department of General Surgery, School of Medicine, South China University of Technology, Guangzhou, 510006, China. zhenyacy@163.com.
  • 7 Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China. zhenyacy@163.com.
  • 8 The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China. zhenyacy@163.com.
  • # Contributed equally.
PMID: 39891171 DOI: 10.1186/s12967-025-06156-4
Abstract

Background: Breast Cancer exhibits high incidence and mortality among women, with distant metastasis, especially bone metastasis, being the leading cause of death. Despite advances in Adjuvant therapies, bone metastasis remains a challenge for patient survival and quality of life. Exosomes, small vesicles capable of mediating intercellular communication, play a crucial role in tumor metastasis.

Results: This study investigated the role of tumor-derived exosomal long noncoding RNA (lncRNA)-MIR193BHG in breast Cancer bone metastasis. LncRNA-MIR193BHG was delivered to osteoclasts via exosomes and promoted osteoclast formation and activity by targeting the miR-489-3p/DNA Methyltransferase 3A (DNMT3A) signaling axis, thereby accelerating breast cancer-induced osteolysis. Knockdown experiments demonstrated that reducing the levels of exosomal lncRNA-MIR193BHG significantly inhibited osteoclast differentiation and bone resorption, which was confirmed both in vitro and in vivo. Additionally, mechanistic studies revealed that lncRNA-MIR193BHG acted as a competitive endogenous RNA (ceRNA) interacting with miR-489-3p, regulating DNMT3A expression and subsequently affecting osteoclast differentiation.

Conclusions: These findings suggest that lncRNA-MIR193BHG plays a critical regulatory role in breast Cancer bone metastasis, and the lncRNA-MIR193BHG/miR-489-3p/DNMT3A signaling axis could be a potential target for the treatment of breast Cancer bone metastasis. Future studies should further explore the broader applicability of this mechanism and its clinical feasibility.

Keywords

Breast cancer bone metastasis; Exosomes; LncRNA.

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