Department of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
Department of General Surgery, People's Hospital of Tibet Autonomous Region, Tibet, 850000, China.
Sci Rep. 2023 Dec 9;13(1):21814. doi: 10.1038/s41598-023-48591-7.
Metastasis of hepatoblastoma (HB) is a key factor that impairs the prognosis and treatment of children. The suppressor of cytokine signaling 2 (SOCS2) is a classical negative feedback protein that regulates cytokine signal transduction and has been known to be downregulated in several tumor, but the molecular mechanisms of its involvement in HB metastasis are unknown. We found that SOCS2 was a gene down-regulated in hepatoblastoma and associated with HB metastasis through bioinformatics. The qRT-PCR, Western blot and IHC showed that SOCS2 was significantly lower in HB tissues. Clinicopathological correlation analysis revealed that low expression of SOCS2 was significantly correlated with tumor metastasis (P = 0.046) and vascular invasion (P = 0.028), associated with poor prognosis. Overexpression of SOCS2 inhibited the migration and invasion of hepatoblastoma cells, while knockdown of SOCS2 expression promoted these malignant phenotypes. In vivo studies revealed overexpression of SOCS2 inhibited the formation of lung metastasis. Up-regulation of SOCS2 in HB cell inhibited EMT and JAK2/STAT5. Conversely, down-regulation of SOCS2 promoted EMT and JAK2/STAT5. The addition of the JAK2 inhibitor Fedratinib partially reversed the effects of si-SOCS2 on HB cells. SOCS2 may inhibit the migration and invasion of HB cells by inhibiting the JAK2/STAT5 signaling pathway. These results may provide guiding significance for the clinical treatment of HB.
肝癌转移是影响儿童预后和治疗的关键因素。细胞因子信号转导抑制因子 2（SOCS2）是一种经典的负反馈蛋白，可调节细胞因子信号转导，已知在几种肿瘤中下调，但 SOCS2 参与肝癌转移的分子机制尚不清楚。我们通过生物信息学发现 SOCS2 是肝癌中下调的基因，并与肝癌转移相关。qRT-PCR、Western blot 和 IHC 显示 SOCS2 在肝癌组织中显著降低。临床病理相关性分析表明，SOCS2 低表达与肿瘤转移（P=0.046）和血管侵犯（P=0.028）显著相关，与预后不良相关。SOCS2 的过表达抑制肝癌细胞的迁移和侵袭，而 SOCS2 表达的下调促进这些恶性表型。体内研究表明 SOCS2 的过表达抑制了肺转移的形成。HB 细胞中 SOCS2 的上调抑制了 EMT 和 JAK2/STAT5。相反，SOCS2 的下调促进了 EMT 和 JAK2/STAT5。添加 JAK2 抑制剂 Fedratinib 部分逆转了 si-SOCS2 对 HB 细胞的影响。SOCS2 可能通过抑制 JAK2/STAT5 信号通路抑制 HB 细胞的迁移和侵袭。这些结果可能为 HB 的临床治疗提供指导意义。
