title: MicroRNA-186 targets Yes-associated protein 1 to inhibit Hippo signaling and tumorigenesis in hepatocellular carcinoma.
abstract: Liver cancer, particularly hepatocellular carcinoma (HCC), is one of leading causes of cancer-related mortality worldwide. Upregulation of the evolutionary conserved Hippo signaling pathway has been observed in HCC patients, and Yes-associated protein 1 (YAP1) has been reported to play a key role in HCC tumorigenesis. microRNAs (miRNAs) are a family of small non-coding RNAs, usually 21-25 nucleotides in length, and are essential in the regulation of gene expression. Abnormal miRNA expression has been implicated in the initiation and progression of numerous forms of cancers, including liver cancer. Here, we report the identification of a novel miRNA, miR-186, and its functions as an HCC tumor suppressor. We observed that miR-186 was downregulated in several HCC cell lines, and that it directly targets YAP1 mRNA. Overexpression of miR-186 in HCC cells significantly downregulates YAP1 mRNA and protein levels, leading to downregulation of the Hippo signaling pathway, which in turn severely inhibits HCC cell migration, invasion and proliferation. Our study is the first to report the direct involvement of miR-186 in downregulating YAP1 and, more significantly, inhibiting HCC tumorigenesis, and supports the role miR-186 as a potential therapeutic target in treating liver cancer.
authors.affiliation: Department of Oncology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Tingyan
authors.initials: T
authors.lastname: Ruan
authors.affiliation: Department of Oncology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Thoracic Surgery, The Second People's Hospital of Wuxi, Wuxi, Jiangsu 214002, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Oncology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Hang
keywords: Hippo signaling; Yes-associated protein 1; hepatocellular carcinoma; miR-186; tumorigenesis