Department of Orthopedics, Air Force Medical Center of PLA, Beijing, China.
The 9th Clinical College, PKU, Beijing, China; Department of Interventional Therapy, Beijing Shijitan Hospital, Capital Medical University, PKU, Beijing, China.
Pathol Res Pract. 2023 May;245:154485. doi: 10.1016/j.prp.2023.154485. Epub 2023 Apr 25.
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.
肝癌骨转移导致预后较差，临床上尚无合适的治疗方法。外泌体与肿瘤骨转移有关。本研究旨在探讨肝癌细胞来源的外泌体对骨转移的影响。从 Hep3B 细胞中分离出外泌体，通过 TRAP 检测评估破骨细胞分化的影响。通过 qRT-PCR 评估 OPG 和 RANKL 的表达。通过荧光素酶报告分析、RNA 下拉和 qRT-PCR 分析 miR-574-5p 和 BMP2 的相互作用。我们发现 Hep3B 细胞通过分泌外泌体促进 RANKL 诱导的 Raw264.7 细胞的破骨细胞分化，导致 OPG 表达降低和 RANKL 表达增加。从 Hep3B 细胞中分离出外泌体，促进破骨细胞分化。外泌体 miR-574-5p 通过靶向 BMP2 促进破骨细胞生成。此外，外泌体通过调节体内 miR-574-3p 促进破骨细胞分化，从而促进骨转移。总之，肝癌细胞来源的外泌体 miR-574-5p 通过调节 BMP2 促进破骨细胞生成，从而促进体内骨转移。这些发现表明，肝癌细胞释放的外泌体是治疗骨转移肝癌的潜在方法。数据可用性声明：本研究中使用和分析的数据集可根据合理要求向相应作者索取。
