Zu Chao, Liu Shizhang, Cao Wei, Liu Zongzhi, Qiang Hui, Li Yong, Cheng Chong, Ji Le, Li Jianhui, Li Jingyuan
Department of Surgical Oncology, Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi Province, P.R. China.
Department of Orthopaedics, Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi Province, P.R. China.
Oncotarget. 2017 May 23;8(21):34698-34708. doi: 10.18632/oncotarget.16150.
The functional roles and clinical significances of miR-590-3p in ICC remain unclear. In the current study, we investigated the expression of miR-590-3p in tissues and sera of ICC by real-time quantitative polymerase chain reaction. We found miR-590-3p was significantly down-regulated in the sera and tissues of ICC patients, especially in those patients with lymph node metastasis or distant metastasis. AUC curves and Cox proportional hazards mode revealed serum miR-590-3p could be novel diagnostic and prognostic biomarker for ICC patients. MiR-590-3p dramatically suppressed epithelial-mesenchymal transition, cell migration, and invasion of ICC cells. SIP1 was identified as direct and functional target of miR-590-3p in ICC cells by luciferase assays. Finally, we found SIP1 expression was inversely correlated with miR-590-3p and closely related to diminished survival in ICC patients. These findings reveal functional and mechanistic roles of miR-590-3p and EMT activator SIP1 in the pathogenesis of ICC.
miR-590-3p在肝内胆管癌(ICC)中的功能作用和临床意义仍不清楚。在本研究中,我们通过实时定量聚合酶链反应研究了miR-590-3p在ICC组织和血清中的表达。我们发现,miR-590-3p在ICC患者的血清和组织中显著下调,尤其是在那些有淋巴结转移或远处转移的患者中。AUC曲线和Cox比例风险模型显示,血清miR-590-3p可能是ICC患者新的诊断和预后生物标志物。miR-590-3p显著抑制ICC细胞的上皮-间质转化、细胞迁移和侵袭。通过荧光素酶测定,SIP1被确定为ICC细胞中miR-590-3p的直接功能靶点。最后,我们发现SIP1表达与miR-590-3p呈负相关,且与ICC患者生存率降低密切相关。这些发现揭示了miR-590-3p和上皮-间质转化激活因子SIP1在ICC发病机制中的功能和作用机制。