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肿瘤来源的外泌体长链非编码RNA-MIR193BHG通过靶向破骨细胞中的miR-489-3p/DNMT3A信号轴促进乳腺癌骨转移。

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

作者信息

Liu Xiaoya, Ma Rui, Wei Feng, Wang Maihuan, Jiang Yiwei, Zheng Peng, Cao Zhen

机构信息

Department of General Surgery, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, 100048, China.

Department of General Surgery, School of Medicine, South China University of Technology, Guangzhou, 510006, China.

出版信息

J Transl Med. 2025 Jan 31;23(1):142. doi: 10.1186/s12967-025-06156-4.

DOI:10.1186/s12967-025-06156-4
PMID:39891171
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11786480/
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.

摘要

背景

乳腺癌在女性中具有高发病率和死亡率，远处转移，尤其是骨转移，是主要的死亡原因。尽管辅助治疗取得了进展，但骨转移仍然是患者生存和生活质量的一大挑战。外泌体是能够介导细胞间通讯的小囊泡，在肿瘤转移中起关键作用。

结果

本研究调查了肿瘤来源的外泌体长链非编码RNA（lncRNA）-MIR193BHG在乳腺癌骨转移中的作用。LncRNA-MIR193BHG通过外泌体传递至破骨细胞，并通过靶向miR-489-3p/DNA甲基转移酶3A（DNMT3A）信号轴促进破骨细胞的形成和活性，从而加速乳腺癌诱导的骨溶解。敲低实验表明，降低外泌体lncRNA-MIR193BHG的水平可显著抑制破骨细胞分化和骨吸收，这在体外和体内均得到证实。此外，机制研究表明，lncRNA-MIR193BHG作为竞争性内源RNA（ceRNA）与miR-489-3p相互作用，调节DNMT3A表达，进而影响破骨细胞分化。

结论

这些发现表明lncRNA-MIR193BHG在乳腺癌骨转移中起关键调节作用，lncRNA-MIR193BHG/miR-489-3p/DNMT3A信号轴可能是治疗乳腺癌骨转移的潜在靶点。未来的研究应进一步探索该机制的更广泛适用性及其临床可行性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/b8af421db06a/12967_2025_6156_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/5c8125d65777/12967_2025_6156_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/bfd273d27f22/12967_2025_6156_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/1ac9adc45ea8/12967_2025_6156_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/92231cacfd14/12967_2025_6156_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/7183984aad9c/12967_2025_6156_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/445a934b6e77/12967_2025_6156_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/9f0c2f00b30a/12967_2025_6156_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/5aa2ce252aef/12967_2025_6156_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/b8af421db06a/12967_2025_6156_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/5c8125d65777/12967_2025_6156_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/bfd273d27f22/12967_2025_6156_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/1ac9adc45ea8/12967_2025_6156_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/92231cacfd14/12967_2025_6156_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/7183984aad9c/12967_2025_6156_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/445a934b6e77/12967_2025_6156_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/9f0c2f00b30a/12967_2025_6156_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/5aa2ce252aef/12967_2025_6156_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/841c/11786480/b8af421db06a/12967_2025_6156_Fig9_HTML.jpg

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