SNORA74B gene silencing inhibits gallbladder cancer cells by inducing PHLPP and suppressing Akt/mTOR signaling

摘要: // Yiyu Qin 1, 2, 3, 4, * , Li Meng Yang Fu 5 Zhiwei Quan 3 Mingzhe Ma Weng Zhengdong Zhang 4 Cuixiang Gao 2 Xinghua Shi Koulan Han 1 Clinical College, Yancheng Institute of Health Sciences, Yancheng, Jiangsu 224000, China Research Centre Biomedical Technology, Department General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School Medicine, 200092, Environmental Genomics, Key Laboratory Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Personalized Nanjing Medical University, 210029, Gastrointestinal The First Zhengzhou Zhengzhou, Henan 450052, These authors have contributed equally this work Correspondence to: Qin, email: qyy128@163.com Zhang, zdzhang@njmu.edu.cn Han, hkl414@163.com Keywords: gallbladder cancer, SNORA74B, PHLPP, snoRNA, AKT Received: October 04, 2016     Accepted: January 08, 2017     Published: February 13, 2017 ABSTRACT Small nucleolar RNAs (snoRNAs) been implicated in the development many cancers. We therefore examined differential expression snoRNAs between cancer (GBC) tissues matched adjacent non-tumor using microarray analysis with confirmation by quantitative real-time PCR (qRT-PCR). Western blot showed that SNORA74B levels were higher GBC than tissues. was positively associated local invasion, advanced TNM stage, CA19-9 level, Ki67 patients GBC, while it negatively an endogenous Akt inhibitor. Moreover, prognostic for overall survival (OS) disease-free (DFS). Functional studies revealed silencing cells sh-SNORA74B suppressed cell proliferation, induced G1 arrest, promoted apoptosis. Preliminary molecular investigation inhibited activation AKT/mTOR signaling pathway, increasing PHLPP expression. depletion shRNA abrogated suppression indicating antitumor effects mediated PHLPP. findings define important role cycle, apoptosis suggest may serve as a novel target treatment.