Dysregulated lncRNA-UCA1 contributes to the progression of gastric cancer through regulation of the PI3K-Akt-mTOR signaling pathway

Abstract

// Chengyun Li 1 , Geyu Liang 1 , Sheng Yang 1 , Jing Sui 1 , Wenzhuo Yao 1 , Xian Shen 1 , Yanqiu Zhang 1 , Hui Peng 1 , Weiwei Hong 1 , Siyi Xu 1 , Wenjuan Wu 1 , Yancheng Ye 2 , Zhiyi Zhang 2 , Wenhua Zhang 2 , Lihong Yin 1 and Yuepu Pu 1 1 Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, P.R. China 2 Gansu Wuwei Tumor Hospital, Wuwei, Gansu 733000, P.R. China Correspondence to: Geyu Liang, email: lianggeyu@163.com Keywords: gastric cancer, lncRNA, UCA1, progression, molecular mechanism Received: March 10, 2017      Accepted: June 12, 2017      Published: July 17, 2017 ABSTRACT The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been recently shown to be dysregulated during disease occurrence and to play an important role in the progression of several cancers. However, the biological role and potential regulation mechanism of UCA1 in the carcinogenesis of gastric cancer remain unclear. In the present study, we found that UCA1 was aberrantly upregulated in gastric cancer tissues and gastric cancer cell lines, and was associated with TNM stage and metastasis. UCA1 silencing significantly inhibited gastric cancer BGC-823 cell proliferation and increased its apoptosis. We also found that UCA1 played an important role in the migration and invasion of gastric cancer cells in vitro and in vivo . The molecular mechanism of UCA1 suggested that UCA1 regulates the PI3K-Akt-mTOR signaling proteins and their downstream mediators, to alter gastric cancer progression in vitro and in vivo . Collectively, the results showed a pivotal role of UCA1 in the tumorigenesis of gastric cancer. In addition, the study characterized a novel lncRNA-mRNA regulatory network, which may lead to a better understanding of the pathogenesis of gastric cancer and assist in lncRNA-directed diagnosis and therapy for this malignancy.