LINC01410-miR-532-NCF2-NF-kB feedback loop promotes gastric cancer angiogenesis and metastasis
Authors: Chen-Yuan Wang
Hui-Wen Weng
Sui Peng
Cui Chen
Zhi-Wei Zhou
Sheng Ye
Yi Xu
Ming Kuang
Ying Gao
Zhen-Hua Chen
Zhou-San Zheng
Xiao-Peng Tian
Dong-Liang Chen
Jia-Xing Zhang
Dan Xie
Journal: Oncogene (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: non-coding RNAs; miR-532-5p; lncRNA; gastric cancer; tumor suppressor
Affiliations: Department of Oncology & Department of Gastroenterology and Hepatology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China., The State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China., Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China., Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China., Department of Gastric and Pancreatic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China., Division of Interventional Ultrasound, Department of Medical Ultrasound, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China., The State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. ., Department of Oncology & Department of Gastroenterology and Hepatology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. .

Abstract:  Dysregulation of non-coding RNAs, including miRNAs and lncRNAs has been reported to play vital roles in gastric cancer (GC) carcinogenesis, but the mechanism involved is largely unknown. Using the cancer genome atlas (TCGA) data set and bioinformatics analyses, we identified miR-532-5p as a potential tumor suppressor in GC, and found that lncRNA LINC01410 might be a negative regulator of miR-532-5p. We then conducted a series of in vivo and in vitro assays to explore the effect of LINC01410 on miR-532-5p-mediated GC malignancy and the underlying mechanism involved. MiR-532-5p overexpression inhibited GC metastasis and angiogenesis in vitro and in vivo, whereas miR-532-5p silencing had the opposite effect. Further study showed that miR-532-5p attenuated NF-κB signaling by directly inhibiting NCF2 expression, while miR-532-5p silencing in GC enhanced NF-κB activity. Furthermore, we demonstrated miR-532-5p down-regulation was caused by aberrantly high expression of LINC01410 in GC. Mechanistically, overexpression of LINC01410 promoted GC angiogenesis and metastasis by binding to and suppressing miR-532-5p, which resulted in up-regulation of NCF2 and sustained NF-κB pathway activation. Interestingly, NCF2 could in turn increase the promoter activity and expression of LINC01410 via NF-κB, thus forming a positive feedback loop that drives the malignant behavior of GC. Finally, high expression of LINC01410, along with low expression of miR-532-5p, was associated with poor survival outcome in GC patients. Our studies uncover a mechanism for constitutive LINC1410-miR-532-5p-NCF2-NF-κB feedback loop activation in GC, and consequently, as a potential therapeutic target in GC treatment. 

Retracted: No

PubPeer comments:
 The same actin control (red boxes) has been used in two different articles by the same group: ![file] , 
 #1 I wish to point out that this issue may mean two things: 1) either for one of the two experiments no control was set, or 2) It could mean the authors only ever performed one single experiment for mRNA expression in different Arabidopsis organs, thus the need for re-use of actin control in two different articles. Could the authors please clarify? ,