Cai Qiang, Wang Zhenqiang, Wang Shouhua, Weng Mingzhe, Zhou Di, Li Chen, Wang Jiandong, Chen Erzhen, Quan Zhiwei
Department of General Surgery, XinHua Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200092, People's Republic of China.
Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200025, People's Republic of China.
Open Biol. 2017 Jan;7(1). doi: 10.1098/rsob.160247.
Long non-coding RNA LINC00152 had been reported as an oncogene in gastric and hepatocellular cancer. In this study, we show that LINC00152 is overexpressed in gallbladder cancer (GBC) tissue samples and cell lines. The high LINC00152 levels correlated negatively with the overall survival time in GBC patients. Functionally, LINC00152 dramatically promoted cell migration, invasion and epithelial-mesenchymal transition (EMT) progression in vitro. In vivo, LINC00152 overexpression significantly promoted tumour peritoneal spreading and metastasis. Mechanistic analyses indicated that LINC00152 functions as a molecular sponge for miR-138, which directly suppresses the expression of hypoxia inducible factor-1α (HIF-1α). We revealed that miR-138 is a suppressor of GBC cell metastasis and EMT progression, and a similar phenomenon was observed in HIF-1α knockdown NOZ cells. Through binding to miR-138, LINC00152 has an oncogenic effect on GBC. Overall, our study suggested that the LINC00152/miR-138/HIF-1α pathway potentiates the progression of GBC, and LINC00152 may be a novel therapeutic target.
长链非编码RNA LINC00152在胃癌和肝细胞癌中已被报道为一种癌基因。在本研究中，我们发现LINC00152在胆囊癌（GBC）组织样本和细胞系中过表达。LINC00152的高表达水平与GBC患者的总生存时间呈负相关。在功能上，LINC00152在体外显著促进细胞迁移、侵袭和上皮-间质转化（EMT）进程。在体内，LINC00152过表达显著促进肿瘤腹膜播散和转移。机制分析表明，LINC00152作为miR-138的分子海绵，直接抑制缺氧诱导因子-1α（HIF-1α）的表达。我们发现miR-138是GBC细胞转移和EMT进程的抑制因子，在HIF-1α敲低的NOZ细胞中也观察到类似现象。通过与miR-138结合，LINC00152对GBC具有致癌作用。总体而言，我们的研究表明LINC00152/miR-138/HIF-1α通路促进GBC的进展，LINC00152可能是一个新的治疗靶点。
