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MiR-21 promotes intrahepatic cholangiocarcinoma proliferation and growth in vitro and in vivo by targeting PTPN14 and PTEN

2015; Impact Journals LLC; Volume: 6; Issue: 8 Linguagem: Inglês

10.18632/oncotarget.3465

1949-2553

Lijuan Wang, Chenchen He, Xin Sui, Mengjiao Cai, Congya Zhou, Jinlu Ma, Lei Wu, Hao Wang, Suxia Han, Qing Zhu,

MicroRNA in disease regulation

// Li-Juan Wang 1 , Chen-Chen He 1 , Xin Sui 1 , Meng-Jiao Cai 1 , Cong-Ya Zhou 1 , Jin-Lu Ma 1 , Lei Wu 1,2 , Hao Wang 1,2 , Su-Xia Han 1 and Qing Zhu 1 1 Department of Oncology, the First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi Province, P.R. China 2 Center of Radiotherapy, Shaanxi Provincial Tumor Hospital, Shaanxi Province, P.R. China Correspondence to: Qing Zhu, email: // Keywords : Intrahepatic cholangiocarcinoma, miR-21, PTPN14, PTEN, tumorigenesis Received : November 07, 2014 Accepted : January 20, 2015 Published : February 28, 2015 Abstract Intrahepatic cholangiocarcinoma (ICC) constitutes the second-most common primary hepatic malignancy. MicroRNAs (miRNAs) play important roles in the pathogenesis of ICC. However, the clinical significance of miR-21 levels in ICC remains unclear. Here, we investigated the role of miR-21 in ICC and found that its expression was significantly upregulated in serum of ICC patients. Serum miR-21 levels robustly distinguished ICC patients from control subjects. Further experiments showed that inhibition of miR-21 suppressed ICC cell proliferation in vitro and tumor growth in vivo . Specifically, inhibition of miR-21 induced cell cycle arrest and apoptosis. Moreover, PTPN14 and PTEN were identified as direct and functional targets of miR-21. Finally, we showed high expression levels of miR-21 were closely related to adverse clinical features, diminished survival, and poor prognosis in ICC patients. This study revealed functional and mechanistic links between miR-21 and tumor suppressor genes, PTPN14 and PTEN , in the pathogenesis of ICC. MiR-21 not only plays important roles in the regulation of cell proliferation and tumor growth in ICC, but is also a diagnostic and prognostic marker, and a potential therapeutic target for ICC.