WGCNA Co-Expression Network Analysis Reveals ILF3-AS1 Functions as a CeRNA to Regulate PTBP1 Expression by Sponging miR-29a in Gastric Cancer.

Zhen-Hu Ren,Kun Wu,Chuan-Yu Hu,Tong Ji,Gao-Pan Shang

doi:10.3389/fgene.2020.00039

Abstract

Gastric cancer (GC) is one of the most common types of human cancers worldwide. However, the detail mechanisms underlying GC progression remained to be investigated. The present study identified 2823 differently expressed mRNAs and 441 differently expressed lncRNAs in GC. WGCNA was conducted to identify highly correlated lncRNAs and mRNAs. Bioinformatics analysis observed that these dysregulated lncRNAs were significantly associated with the regulation of angiogenesis, cell division, cell-cell adhesion, blood vessel development, adaptive immune response, gastric acid secretion, immune response. Co-expression analysis identified ILF3-AS1 was a key lncRNA involved in regulating GC progression. Loss of function assays showed that knockdown of ILF3-AS1 significantly suppressed GC cell proliferation and metastasis. Mechanically, the results indicate that ILF3-AS1 could enhance PTBP3 expression as an miR-29a sponge, thereby promoting the proliferation and metastasis of GC cells. Our work suggests that the ILF3-AS1/miR-29a/PTBP3 axis may be a potential target for the clinical diagnosis and treatment of GC.

Highlights

Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide (Stock and Otto, 2005; Nobili et al, 2011)
We identified 1358 up-regulated mRNAs and 1465 down-regulated mRNAs in GC samples compared to normal tissues samples
The results showed that a high expression of ILF3-AS1 was significantly negatively correlated with the disease free survival (DFS) (Figure 4B–C) in GC

Summary

Introduction

Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide (Stock and Otto, 2005; Nobili et al, 2011). GC is one of the most common gastrointestinal cancers in China (Wang and Shou, 2014). A series of regulators were revealed to be associated with the progression of GC, including HER2, TP53 and NF-kB1. Loss of NFkB1 causes GC with aberrant inflammation and expression of immune checkpoint regulators in a STAT-1-Dependent Manner (O'Reilly et al, 2018). The prognosis for advanced stage GC patients remains poor (Im et al, 2011). The 5-year survival rate is about 20%–30% (Ajani et al, 1991)

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Discussion

Conclusion