Abstract
Background & AimsAberrant expression of microRNAs is associated with many cancers progression. Many studies have shown that miR-16 is down-regulated in many cancers. However, its role in cholangiocarcinoma (CCA) is unknown.MethodsQuantitative real-time PCR (qRT-PCR) was developed to measure miR-16 expression in CCA tissues and cell lines. CCK-8, colony formation and transwell assays were used to reveal the role of miR-16 in CCA cell proliferation and malignant transformation in vitro. The loss-and-gain function was further validated by subcutaneous xenotransplantation and tail vein injection xenotransplantation model in vivo. Dual-luciferase reporter assay was performed to validate the relationship of miR-16 with YAP1.ResultsMiR-16 was notably downregulated in CCA tissues, which was associated with tumor size, metastasis, and TNM stage. Both in vitro and in vivo studies demonstrated that miR-16 could suppress proliferation, invasion and metastasis throughout the progression of CCA. We further identified YAP1 as a direct target gene of miR-16 and found that miR-16 could regulate CCA cell growth and invasion in a YAP1-dependent manner. In addition, YAP1 was markedly upregulated in CCA tissues, which was reversely correlated with miR-16 level in tissue samples. Besides, Down-regulation of miR-16 was remarkably associated with tumor progression and poor survival in CCA patients through a Kaplan–Meier survival analysis.ConclusionsmiR-16, as a novel tumor suppressor in CCA through directly targeting YAP1, might be a promising therapeutic target or prognosis biomarker for CCA.
Highlights
Cholangiocarcinoma (CCA) is a highly aggressive tumor derived from bile duct epithelial cells
MiR-16 was notably downregulated in CCA tissues, which was associated with tumor size, metastasis, and TNM stage
Both in vitro and in vivo studies demonstrated that miR-16 could suppress proliferation, invasion and metastasis throughout the progression of CCA
Summary
Cholangiocarcinoma (CCA) is a highly aggressive tumor derived from bile duct epithelial cells. The survival rate and prognosis of patients with CCA is dismal on account of the early invasion and metastasis [3]. Lots of miRNAs play a pivotal role in tumorigenesis such as cell proliferation, migration, invasion, apoptosis, and metastasis [9,10,11,12]. As is known to all, the tumor suppressor miR-16 is observably decreased and its function has been studied all the time in different cancers, including lung cancer, osteosarcoma, breast cancer, glioma, laryngeal carcinoma and so on [13,14,15]. Many studies have shown that miR-16 is down-regulated in many cancers. Its role in cholangiocarcinoma (CCA) is unknown
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