The novel lncRNA p4516 acts as a prognostic biomarker promoting gastric cancer cell proliferation and metastasis
Received 16 January 2019
Accepted for publication 5 April 2019
Published 12 June 2019 Volume 2019:11 Pages 5375—5391
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Dr Kenan Onel
Meng-Lin Nie,1 Jing Han,1 Han-Chen Huang,2,3 Ting Guo,1 Long-Tao Huangfu,1 Xiao-Jing Cheng,1 Xiao-Mei Li,1 Hong Du,1 Qing-Da Li,1 Xian-Zi Wen,1 Jia-Fu Ji1,4
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 2Key Laboratory of RNA Biology, Beijing Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People’s Republic of China; 3Centre for Cognitive Machines and Computational Health (CMaCH), The School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Department of Gastrointestinal Surgery, Peking University Cancer Hospital, Beijing, People’s Republic of China
Purpose: Emerging evidence has shown that long noncoding RNAs (lncRNAs) participate in oncogenesis and tumor progression. We previously found a novel lncRNA p4516 which was closely associated with prognosis by preliminary study of lncRNA expression profile from paired tumors and nontumor tissues in 198 gastric cancer (GC) patients. However, the exact biological functions and the underlying molecular mechanisms of p4516 in gastric tumorigenesis still remain unclear.
Materials and methods: The RNA fluorescence in situ hybridization (RNA-FISH) analysis, cytoplasmic and nuclear RNA isolation and qRT-PCR were applied to determine the subcellular localization of p4516. Expression levels of p4516 were assessed using qRT-PCR in both GC cell lines and in 142 primary GC tissues. Correlations between p4516 expression and GC patients’ clinicopathological parameters were analyzed. Gain- and loss-of-function experiments were employed to investigate the role of p4516 in proliferation, migration and invasion both in vitro and in vivo. In addition, Western blotting and immunohistochemical staining were used to examine the protein expression levels.
Results: LncRNA p4516 was mainly localized in the nucleus of GC cells and p4516 tended to have higher expression levels in GC cells compared to the normal gastric mucosa-derived cells GES-1. Furthermore, higher expression levels of p4516 correlated with worse clinical outcomes in GC patients and acted as an independent prognostic biomarker. Functional analysis revealed that p4516 participated in the regulation of GC cell proliferation, invasion and migration both in vivo and in vitro. Moreover, p4516 was involved in epithelial–mesenchymal transition (EMT) in GC cells.
Conclusion: Our study demonstrated the oncogenic role of novel lncRNA p4516 in the gastric carcinogenesis for the first time. High expression of p4516 may act as prognostic marker in patient with gastric cancer.
Keywords: LncRNA, p4516, Gastric cancer, EMT
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