Abstract
Deregulated lncRNAs play critical roles in tumorigenesis and tumor progression. NR2F1-AS1 is an antisense lncRNA of NR2F1. However, the biological function of NR2F1-AS1 in gastric cancer (GC) remains largely unclear. In this study, we revealed that NR2F1-AS1 and NR2F1 were both positively correlated with the degree of malignancy and predicted poor prognosis in two independent GC cohorts. Besides, NR2F1-AS1 and NR2F1 can respond to Epithelial-to-mesenchymal transition (EMT) signaling in GC, since their expression was increased by TGF-beta treatment and decreased after stable overexpression of OVOL2 in GC cell lines. NR2F1-AS1 and NR2F1 were highly co-expressed in pan-tissues and pan-cancers. Depletion of NR2F1-AS1 compromised the expression level of NR2F1 in GC cells. Furthermore, NR2F1-AS1 knockdown inhibited the proliferation, migration, invasion and G1/S transition of GC cells. More importantly, transcriptome sequencing revealed a novel ceRNA network composed of NR2F1-AS1, miR-29a-3p, and VAMP7 in GC. The overexpression of VAMP7 predicted poor prognosis in GC. Rescue assay confirmed that NR2F1-AS1 promotes GC progression through miR-29a-3p/VAMP7 axis. Our finding highlights that the aberrant expression of NR2F1-AS1 is probably due to the abnormal EMT signaling in GC. LncRNA NR2F1-AS1 plays crucial roles in GC progression by modulating miR-29a-3p/VAMP7 axis, suggesting that NR2F1-AS1 may serve as a potential therapeutic target in GC.
Highlights
Gastric cancer (GC) is a heterogeneous tumor with the fourth highest mortality rate worldwide [1]
We identified an antisense lncRNA NR2F1-AS1 that induced by Epithelial-to-mesenchymal transition (EMT) in GC
NR2F1-AS1 and NR2F1 are clinically correlated with poor prognosis in GC NR2F1-AS1 is an antisense lncRNA of NR2F1, known as COUP Transcription Factor I (COUPTF1, Fig. 1a)
Summary
Gastric cancer (GC) is a heterogeneous tumor with the fourth highest mortality rate worldwide [1]. In 2015, Cristescu et al have reported that GC patients with EMT molecular subtype possess worst prognosis [5]. Once the EMT program is started, remarkable changes would be observed in the expression of the EMT-related genes [11, 12]. These EMTrelated genes eventually have a profound effect on cell morphology and function [13, 14]. Most of the existing research focuses on the coding genes caused by EMT, and the biological functions of EMT-related lncRNA are relatively rarely reported
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