miR-181b-5p/SOCS2/JAK2/STAT5 axis facilitates the metastasis of hepatoblastoma  

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作  者:Yong Lv Xiaolong Xie Guoyou Zou Meng Kong Jiayin Yang Jing Chen Bo Xiang 

机构地区:[1]Department of Pediatric Surgery and Laboratory of Pediatric Surgery,West China Hospital,Sichuan University,Chengdu 610041,China [2]Department of General Surgery,People’s Hospital of Tibet Autonomous Region,Tibet 850000,China [3]Department of Pediatric Surgery,Children’s Hospital Affiliated to Shandong University,Jinan 250022,China [4]Liver Transplantation Center,Department of General Surgery,West China Hospital,Sichuan University,Chengdu 610041,China

出  处:《Precision Clinical Medicine》2023年第4期189-199,共11页精准临床医学(英文)

基  金:supported by Scientific Research Starting Foundation for Introduced Talents(to Jing Chen);Sichuan Science and Technology Department(Grants No.2022NSFSC1301&2020YFS0108);1·3·5 project for disciplines of excellence,West China Hospital,Sichuan University(Grants No.ZYJC18003,2021HXFH020);Shandong Provincial Natural Science Foundation(Grant No.ZR2022MH229).

摘  要:Introduction:Hepatoblastoma(HB)is a malignant liver tumor predominantly found in children and tumor metastasis is one of the main causes of poor prognosis in affected patients.The precise molecular mechanisms responsible for HB metastasis remain incom-pletely understood.However,there is evidence suggesting a connection between the dysregulation of microRNAs(miRNAs)and the progression of tumor metastasis in HB.Methods:The study utilized weighted gene co-expression network analysis(WGCNA)to analyze a miRNA microarray dataset of HB.The expression of miR-181b-5p in HB tissues and cells was detected using quantitative real-time PCR.The impact of miR-181b-5p on the metastatic capacity of HB was evaluated through scratch and Transwell assays.The effects of exogenously expressing miR-181b on the metastatic phenotypes of HB cells were evaluated in vivo.Furthermore,a luciferase reporter assay was performed to validate a potential target of miR-181b-5p in HB.Results:We found that miR-181b-5p was highly expressed in HB tissues and HB cell lines.Overexpression of miR-181b enhanced scratch healing,cell migration,and invasion abilities in vitro,as well as enhancing HB lung metastasis potential in vivo.Dual-luciferase reporter assays showed that Suppressor Of Cytokine Signaling 2(SOCS2)was a direct target of miR-181b.The overexpression of miR-181b resulted in the suppression of SOCS2 expression,subsequently activating the epithelial-mesenchymal transition and JAK2/STAT5 signaling pathways.The rescue experiment showed that SOCS2 overexpression attenuated the effects of miR-181b on HB cells.Conclusion:Our study showed that miR-181b promotes HB metastasis by targeting SOCS2 and may be a potential therapeutic target for HB.

关 键 词:miR-181b SOCS2 METASTASIS HEPATOBLASTOMA CHILDREN 

分 类 号:R735.7[医药卫生—肿瘤]

 

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