MiR-21 promotes intrahepatic cholangiocarcinoma proliferation and growth in vitro and in vivo by targeting PTPN14 and PTEN
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Li-Juan Wang1, Chen-Chen He1, Xin Sui1, Meng-Jiao Cai1, Cong-Ya Zhou1, Jin-Lu Ma1, Lei Wu1,2, Hao Wang1,2, Su-Xia Han1 and Qing Zhu1
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
Qing Zhu, email:
Keywords: Intrahepatic cholangiocarcinoma, miR-21, PTPN14, PTEN, tumorigenesis
Received: November 07, 2014 Accepted: January 20, 2015 Published: February 28, 2015
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.
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