Abstract
Gastric cancer (GC) is one of the deadliest cancers, and long noncoding RNAs (lncRNAs) have been reported to be the important regulators during the occurrence and development of GC. The present study identified a novel and functional lncRNA in GC, named NR038975, which was confirmed to be markedly upregulated in the Gene Expression Profiling Interactive Analysis (GEPIA) dataset and our independent cohort of GC tissues. We firstly characterized the full-length sequence and subcellular location of NR038975 in GC cells. Our data demonstrated that upregulated NR038975 expression was significantly related to lymph node metastasis and TNM stage. In addition, knockdown of NR038975 inhibited GC cell proliferation, migration, invasion, and clonogenicity and vice versa. Mechanistically, RNA pull-down and mass spectrometry assays identified the NR038975-binding proteins and NF90/NF45 complex, and the binding was also confirmed by RNA immunoprecipitation and confocal experiments. We further demonstrated that genetic deficiency of NR038975 abrogated the interaction between NF45 and NF90. Moreover, NF90 increased the stability of NR038975. Thus, NR038975-NF90/NF45 will be an important combinational target of GC. Finally, we detected NR038975 in serum exosomes and serum of GC patients. Our results indicated that NR038975 was a biomarker for gastric tumorigenesis. The current study demonstrated that NR038975 is a novel lncRNA that is clinically and functionally engaged in GC progression and might be a novel diagnostic marker and potential therapeutic target.
Highlights
Gastric cancer (GC) is one of the most common cancers and has the third highest death rate in the world [1]
Based on our previous Long noncoding RNAs (lncRNAs)/messenger RNA microarray analysis of GC-associated lncRNAs (GSE95667) [36], which contains four pairs of GC tissues and normal tissues, lncRNA NR038975 was significantly upregulated in GC tissues compared with normal tissues (Figure 1A)
We found that NR038975 was highly expressed in GC tissues compared with normal tissues in the Gene Expression Profiling Interactive Analysis (GEPIA) dataset (Figure 1B)
Summary
Gastric cancer (GC) is one of the most common cancers and has the third highest death rate in the world [1]. The molecular mechanisms of lncRNAs on biological functions are diverse and confusing and include serving as microRNA (miRNA) sponges [14, 15], acting as scaffolds to regulate protein–DNA or protein–protein interactions [16, 17], and serving as decoys to bind to proteins [18, 19]. These results demonstrate that lncRNAs significantly regulate tumor progression and could be used as potential therapeutic targets. These results inspire the study of lncRNAs in the treatment of cancer
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