SOCS2 inhibits hepatoblastoma metastasis via downregulation of the JAK2/STAT5 signal pathway
Abstract 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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-48591-7 |
| _version_ | 1797398020455661568 |
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| author | Yong Lv Xiaolong Xie Guoyou Zou Meng Kong Jiayin Yang Jing Chen Bo Xiang |
| author_facet | Yong Lv Xiaolong Xie Guoyou Zou Meng Kong Jiayin Yang Jing Chen Bo Xiang |
| author_sort | Yong Lv |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-09T01:18:42Z |
| format | Article |
| id | doaj.art-89d989503f3f4402947eb6861b574462 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T01:18:42Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-89d989503f3f4402947eb6861b5744622023-12-10T12:17:32ZengNature PortfolioScientific Reports2045-23222023-12-0113111310.1038/s41598-023-48591-7SOCS2 inhibits hepatoblastoma metastasis via downregulation of the JAK2/STAT5 signal pathwayYong Lv0Xiaolong Xie1Guoyou Zou2Meng Kong3Jiayin Yang4Jing Chen5Bo Xiang6Department of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan UniversityDepartment of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan UniversityDepartment of General Surgery, People’s Hospital of Tibet Autonomous RegionDepartment of Pediatric Surgery, Children’s Hospital Affiliated to Shandong UniversityLiver Transplantation Center, Department of General Surgery, West China Hospital, Sichuan UniversityDepartment of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan UniversityDepartment of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan UniversityAbstract 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.https://doi.org/10.1038/s41598-023-48591-7 |
| spellingShingle | Yong Lv Xiaolong Xie Guoyou Zou Meng Kong Jiayin Yang Jing Chen Bo Xiang SOCS2 inhibits hepatoblastoma metastasis via downregulation of the JAK2/STAT5 signal pathway Scientific Reports |
| title | SOCS2 inhibits hepatoblastoma metastasis via downregulation of the JAK2/STAT5 signal pathway |
| title_full | SOCS2 inhibits hepatoblastoma metastasis via downregulation of the JAK2/STAT5 signal pathway |
| title_fullStr | SOCS2 inhibits hepatoblastoma metastasis via downregulation of the JAK2/STAT5 signal pathway |
| title_full_unstemmed | SOCS2 inhibits hepatoblastoma metastasis via downregulation of the JAK2/STAT5 signal pathway |
| title_short | SOCS2 inhibits hepatoblastoma metastasis via downregulation of the JAK2/STAT5 signal pathway |
| title_sort | socs2 inhibits hepatoblastoma metastasis via downregulation of the jak2 stat5 signal pathway |
| url | https://doi.org/10.1038/s41598-023-48591-7 |
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