OncoTargets and Therapy (Oct 2019)
LncRNA NORAD Promotes Proliferation And Inhibits Apoptosis Of Gastric Cancer By Regulating miR-214/Akt/mTOR Axis
Abstract
Wei Tao,1,* Yajun Li,1,* Meng Zhu,2 Cheng Li,3 Peng Li1 1Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan City, Ningxia 750004, People’s Republic of China; 2Department of Gastroenterology, Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710049, People’s Republic of China; 3Department of Gastroenterology, Pingluo County People’s Hospital, Shizuishan City, Ningxia 753400, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei TaoDepartment of Gastroenterology, General Hospital of Ningxia Medical University, No. 804 Shengli Street, Xingqing District, Yinchuan City, Ningxia 750004, People’s Republic of ChinaTel +86-13895475006Email [email protected]: In previous studies, we confirmed that the overexpression of lncRNA NORAD was associated with the occurrence and development of gastric cancer (GC). The aim of the present study was to explore the molecular mechanism of lncRNA NORAD on GC cell proliferation and apoptosis in vitro and in vivo.Patients and methods: The quantitative Real-Time PCR (qRT-PCR) was used to determine the expression levels of lncRNA NORAD and miR-214 in GC tissues and cells. The interaction between lncRNA NORAD and miR-214 was investigated by biological information and Dual-Luciferase gene reporter assay. Effect of lncRNA NORAD on GC tumor growth in vivo was studied in tumor xenograft model mice. The apoptosis of GC cells was determined by flow cytometry. The proliferation of GC cells was determined by 5-ethynyl-2´-deoxyuridine (EDU) and colony formation assays. Western Blot was used to determine the expressions of caspase-3, Akt and mTOR in GC tissues and cells.Results: The qRT-PCR results showed that lncRNA NORAD was highly expressed in human GC tissues and cell lines, while miR-214 was significantly down-regulated. Meanwhile, there was a direct interaction between lncRNA NORAD and miR-214. In addition, lncRNA NORAD could promote the growth and proliferation of GC cells both in vivo and in vitro. NOARD could also inhibit the apoptosis of GC cells by down-regulating caspase-3; however, miR-214 overexpression attenuated this effect. Moreover, lncRNA NORAD promoted the phosphorylation of Akt and mTOR in mouse GC tissues and GC cell lines, while miR-214 mimics inhibited that promotion.Conclusion: These results suggested that NORAD could promote the development of GC by inhibiting miR-214 expression and activating the Akt/mTOR signaling pathway.Keywords: gastric cancer, miR-214, lncRNA NORAD, Akt/mTOR
