PMID- 28915618 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20170925 LR - 20181113 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 8 IP - 34 DP - 2017 Aug 22 TI - Suppression of miR-16 promotes tumor growth and metastasis through reversely regulating YAP1 in human cholangiocarcinoma. PG - 56635-56650 LID - 10.18632/oncotarget.17832 [doi] AB - 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. FAU - Han, Sheng AU - Han S AD - Liver Transplantation Center of The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China. FAU - Wang, Dong AU - Wang D AD - Liver Transplantation Center of The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China. FAU - Tang, Guohua AU - Tang G AD - Liver Transplantation Center of The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China. FAU - Yang, Xinxiang AU - Yang X AD - Liver Transplantation Center of The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China. FAU - Jiao, Chenyu AU - Jiao C AD - Liver Transplantation Center of The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China. FAU - Yang, Renjie AU - Yang R AD - Liver Transplantation Center of The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China. FAU - Zhang, Yaodong AU - Zhang Y AD - Liver Transplantation Center of The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China. FAU - Huo, Liqun AU - Huo L AD - Liver Transplantation Center of The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China. FAU - Shao, Zicheng AU - Shao Z AD - Liver Transplantation Center of The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China. FAU - Lu, Zefa AU - Lu Z AD - Liver Transplantation Center of The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China. FAU - Zhang, Jiawei AU - Zhang J AD - Liver Transplantation Center of The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China. FAU - Li, Xiangcheng AU - Li X AD - Liver Transplantation Center of The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China. LA - eng PT - Journal Article DEP - 20170512 PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 PMC - PMC5593589 OTO - NOTNLM OT - CCA OT - metastasis OT - miRNA OT - prognosis OT - proliferation COIS- CONFLICTS OF INTEREST The authors declare that they have no financial conflicts of interest. EDAT- 2017/09/17 06:00 MHDA- 2017/09/17 06:01 PMCR- 2017/08/22 CRDT- 2017/09/17 06:00 PHST- 2017/01/16 00:00 [received] PHST- 2017/04/19 00:00 [accepted] PHST- 2017/09/17 06:00 [entrez] PHST- 2017/09/17 06:00 [pubmed] PHST- 2017/09/17 06:01 [medline] PHST- 2017/08/22 00:00 [pmc-release] AID - 17832 [pii] AID - 10.18632/oncotarget.17832 [doi] PST - epublish SO - Oncotarget. 2017 May 12;8(34):56635-56650. doi: 10.18632/oncotarget.17832. eCollection 2017 Aug 22.