Research Papers:

Suppression of miR-16 promotes tumor growth and metastasis through reversely regulating YAP1 in human cholangiocarcinoma

Sheng Han, Dong Wang, Guohua Tang, Xinxiang Yang, Chenyu Jiao, Renjie Yang, Yaodong Zhang, Liqun Huo, Zicheng Shao, Zefa Lu, Jiawei Zhang and Xiangcheng Li _

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Oncotarget. 2017; 8:56635-56650. https://doi.org/10.18632/oncotarget.17832

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Sheng Han1,*, Dong Wang1,*, Guohua Tang1,*, Xinxiang Yang1, Chenyu Jiao1, Renjie Yang1, Yaodong Zhang1, Liqun Huo1, Zicheng Shao1, Zefa Lu1, Jiawei Zhang1 and Xiangcheng Li1

1Liver Transplantation Center of The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China

*These authors contributed equally to this work

Correspondence to:

Xiangcheng Li, email: [email protected]

Keywords: CCA, miRNA, proliferation, metastasis, prognosis

Received: January 16, 2017    Accepted: April 19, 2017    Published: May 12, 2017


Background & Aims: Aberrant 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.

Methods: Quantitative 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.

Results: 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. 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.

Conclusions: miR-16, as a novel tumor suppressor in CCA through directly targeting YAP1, might be a promising therapeutic target or prognosis biomarker for CCA.

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