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.
Highlights
Intrahepatic cholangiocarcinoma (ICC) is relatively rare in most populations, but constitutes the second-most common primary hepatic malignancy [1,2,3], with increased worldwide incidence over the past three decades [4, 5]
For the first time, we describe the effects of miR-21 on its potential target genes protein tyrosine phosphatase non-receptor type 14 (PTPN14), and phosphatase and tension homolog (PTEN) in various malignant phenotypes of ICC cells in vitro and in vivo
We found that miR-21 levels were statistically significantly elevated in the sera of ICC patients (P < 0.001; Figure 1C)
Summary
Intrahepatic cholangiocarcinoma (ICC) is relatively rare in most populations, but constitutes the second-most common primary hepatic malignancy [1,2,3], with increased worldwide incidence over the past three decades [4, 5]. The great majority of ICC patients are diagnosed at late clinical stages, when curative surgery is not a viable option [9, 10]. Survival times for these patients is typically measured in months [4, 11,12,13]. Diagnostic techniques are plagued by low specificity in early stage ICC [4]. Given the increased incidence of ICC, its manifest aggressiveness and poor outcomes, further studies clarifying diagnostic and prognostic factors are warranted
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