Published online Nov 28, 2019. doi: 10.3748/wjg.v25.i44.6508
Peer-review started: August 30, 2019
First decision: October 14, 2019
Revised: October 30, 2019
Accepted: November 13, 2019
Article in press: November 13, 2019
Published online: November 28, 2019
Long noncoding RNAs (lncRNAs) are aberrant and play critical roles in gastric cancer (GC) progression and metastasis. Searching for coexpressed lncRNA clusters or representative biomarkers related to malignant phenotypes of GC may help to elucidate the mechanism of tumor development and predict the prognosis of GC.
To investigate the prognostic value of NOTCH1 associated with lncRNA in T cell acute lymphoblastic leukemia 1 (NALT1) in GC and the mechanism of its involvement in GC invasion and metastasis.
RNA sequencing and corresponding clinical data were downloaded from The Cancer Genome Atlas database. The significance module was studied by weighted gene coexpression network analysis. A total of 336 clinical samples were included in the study. Gene silencing, reverse transcription polymerase chain reaction, western blotting, scrape motility assay, and Transwell migration assay were used to assess the function of hub-lncRNAs.
At the transcriptome level, 3339 differentially expressed lncRNAs were obtained. weighted gene coexpression network analysis was used to obtain 15 lncRNA clusters and observe their coexpression. Pearson’s correlation showed that blue module was correlated with tumor grade and survival. NALT1 was the hub-lncRNA of blue module and was an independent risk factor for GC prognosis. NALT1 was overexpressed in GC and its expression was closely related to invasion and metastasis. The mechanism may involve NALT1 regulation of NOTCH1, which is associated with lncRNA in T cell acute lymphoblastic leukemia, through cis regulation, thereby affecting the expression of the NOTCH signaling pathway.
NALT1 is overexpressed and promotes invasion and metastasis of GC. The mechanism may be related to regulation of NOTCH1 by NALT1 and its effect on NOTCH signaling pathway expression.
Core tip: Analysis of the Cancer Genome Atlas and clinical data revealed that the long noncoding RNA (lncRNA) NOTCH1 associated with lncRNA in T cell acute lymphoblastic leukemia 1 (NALT1) was associated with poor prognosis of gastric cancer (GC). We investigated the possible mechanism of this association. We downloaded the Cancer Genome Atlas-Stomach Adenocarcinoma RNA-seq data and identified the differentially expressed lncRNAs. Weighted gene coexpression network analysis was used to clarify the connection between modules and clinical information. We then chose lncRNA NALT1 as the hub-lncRNA of blue-module. NALT1 was overexpressed in GC and promoted invasion and metastasis of GC. The over-expression of NALT1 was linked to poor prognosis in GC. The mechanism may be related to the regulation of NOTCH1 by NALT1 and its effect on the expression of NOTCH signaling pathway.