miR-9-3p plays a tumour-suppressor role by targeting TAZ (WWTR1) in hepatocellular carcinoma cells

被引:101
作者
Higashi, T. [1 ]
Hayashi, H. [1 ]
Ishimoto, T. [1 ]
Takeyama, H. [1 ]
Kaida, T. [1 ]
Arima, K. [1 ]
Taki, K. [1 ]
Sakamoto, K. [1 ]
Kuroki, H. [1 ]
Okabe, H. [1 ]
Nitta, H. [1 ]
Hashimoto, D. [1 ]
Chikamoto, A. [1 ]
Beppu, T. [1 ]
Baba, H. [1 ]
机构
[1] Kumamoto Univ, Grad Sch Med Sci, Dept Surg Gastroenterol, Kumamoto 8608556, Japan
基金
日本学术振兴会;
关键词
microRNA; Hippo pathway; TAZ; hepatocellular carcinoma; YES-ASSOCIATED PROTEIN; HIPPO PATHWAY; CANCER METASTASIS; YAP; PROLIFERATION; INHIBITION; ONCOGENE;
D O I
10.1038/bjc.2015.170
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: The inactivation of the Hippo pathway lead to TAZ (PDZ-binding motif)/YAP (yes-associated protein) overexpression, and is associated with worse prognostic outcomes in various cancers including hepatocellular carcinoma (HCC). Although there are several reports of microRNA (miR) targeting for YAP, miR targeting for TAZ remains unclear. The aim of this study is to identify the miR targeting TAZ expression in HCC. Methods: MicroRNA expression was analysed using the Human miFinder 384HC miScript miR PCR array, and was compared between low and high TAZ expression cell lines. Then, we extracted miR-9-3p as a tumour-suppressor miR targeting TAZ. We examined the functional role of miR-9-3p using miR-9-3p mimic and inhibitor in HCC cell lines). Results: In HCC cell lines and HCC clinical samples, there was the inverse correlation between miR-9-3p and TAZ expressions. TAZ expression was induced by treatment of miR-9-3p inhibitor and was downregulated by treatment of miR-9-3p mimic. Treatment of miR-9-3p mimic inhibited cell proliferative ability with downregulated phosphorylations of Erk1/2, AKT, and beta-catenin in HLF. Inversely, treatment of miR-9-3p inhibitor accelerated cell growth compared with control in HuH1.
引用
收藏
页码:252 / 258
页数:7
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