Long noncoding RNA NEAT1 promotes tumorigenesis in H. pylori gastric cancer by sponging miR‐30a to regulate COX‐2/BCL9 pathway

Abstract

Background: Helicobacter pylori (H. pylori) is a carcinogenic factor for gastric cancer. Our previous study demonstrated that H. pylori decreased the expression of microRNA(miRNA)-30a to promote the tumorigenesis in gastric cancer. However, the upstream regulatory mechanism of miR-30a hasn't wellelucidated. In this study, we found the long non-coding RNA (lncRNA) NEAT1 may sponge miR-30a to regulate COX-2/BCL9 pathway.Methods: The expression of NEAT1 was detected in gastric cancer tissues and tumour adjacent tissues by uorescence in-situ hybridization(FISH) analysis and RT-qPCR. LncRNA-miRNA interaction networks were constructed using the RNAhybird and Starbase v.2.0. and then validated using dual-luciferase assay.The effects of NEAT1 dysregulation on the proliferative, migratory and invasive abilities of H. pylori ltrate infected gastric cancer cells were observed by cell counting kit-8 (CCK-8), colony formation, wound healing test and transwell assays. Western blot and RT-qPCR were performed to detect protein and RNA expression. The Immunohistochemistry(IHC) was carried out to analyze the location and expression of COX-2 and BCL9Results: FISH and RT-qPCR demonstrated that the expression of NEAT1 was up-regulated in gastric cancer tissues, especially in H. pylori gastric cancer tissues, and the expression of NEAT1 is negatively correlated with miR-30a(miR-30a-3p, miR-30a-5p).The proliferation, migration and invasion of H. pylori ltrate infected gastric cancer cells could be largely enhanced by the up-regulation of NEAT1, while the downregulation of NEAT1 decreased these abilities, and miR-30a could reverse the effect of NEAT1 on these abilities. Dual-luciferase assay identi ed that NEAT1 directly targeted miR-30a (miR-30a-3p, miR-30a-5p).Due to miR-30a(miR-30a-3p, miR-30a-5p) negatively regulated the expression of downstream COX-2 and BCL9, NEAT1 was identi ed to indirectly upregulate the expression of COX-2 and BCL9.IHC showed that the expression of COX-2 and BCL9 were increased in H. pylori gastric cancer tissues. Conclusion:The study demonstrated that lncRNA NEAT1 may act as a promoter of tumorigenesis in H. pylori gastric cancer, by sponging miR-30a(miR-30a-3p, miR-30a-5p) to regulate COX-2/BCL9 pathway.

Molecular Interactions of the Long Noncoding RNA NEAT1 in Cancer

“…Studies have shown that NEAT1 can upregulate the expression of ABCC4, JAG1, SOX11, COX-2, etc. These factors will finally promote the proliferation, migration, and invasion of gastric cancer [ 49 , 53 , 54 , 55 ].…”

Upregulation of OTX2-AS1 is Associated With Immune Infiltration and Predicts Prognosis of Gastric Cancer

“… 32 lncRNA NEAT1 may regulate the COX-2/BCL9 pathway by sponging miR-30a (miR-30a-3p and miR-30a-5p) and thus act as a promoter of tumorigenesis in H pylori GC. 33 Although H pylori infection is closely associated with the progression of GC, the mechanisms underlying this process are not fully understood. In this study, OTX2-AS1 expression was significantly negatively associated with H pylori infection in GC patients ( P = .006).…”

In silico analysis to identify novel ceRNA regulatory axes associated with gallbladder cancer

“…Literature search on “lncRNA-miRNA pairs” in cancer revealed one lncRNA (MALAT1) -miR125b interaction in laryngocarcinoma ( Zong et al, 2021 ), three lncRNA (TUG1, NEAT1, MALAT1) -miR-34a interactions reported in endometrial cancer, Nasopharyngeal Cancer, Melanoma ( Liu et al, 2017 ; Ji et al, 2019 ; Li et al, 2019 ) and three lncRNA (PVT1, NEAT1, and MALAT1) -miR-30a-5p interactions in papillary thyroid carcinoma, gastric cancer, Hepatocellular Carcinoma ( Feng et al, 2018 ; Pan et al, 2018 ; Rao et al, 2021 ). Previous studies revealed that the lncRNAs H19 and NEAT1 were found to directly target miR-193a-3p in Hepatocellular Carcinoma and Lung Adenocarcinoma, respectively ( Ma et al, 2018 ; Xiong et al, 2018 ).…”