Abstract
Simple SummaryLong noncoding RNAs (lncRNAs) are important regulators of cell progression or regression in gastric cancer (GC). The lncRNA LOC441461 was downregulated in TNM stage IV GC. The downregulation of LOC441461 promoted the proliferation, cell cycle progression, and metastasis of GC cells in vitro. We confirmed, with predictable targets, that LOC441461 interacts with transcription factors and promotes tumor progression. Our study suggests LOC441461 as a potential biomarker, which could also lead to a therapeutic target in patients with advanced TNM stage gastric cancer.Gastric cancer is a common tumor, with a high mortality rate. The severity of gastric cancer is assessed by TNM staging. Long noncoding RNAs (lncRNAs) play a role in cancer treatment; investigating the clinical significance of novel biomarkers associated with TNM staging, such as lncRNAs, is important. In this study, we investigated the association between the expression of the lncRNA LOC441461 and gastric cancer stage. LOC441461 expression was lower in stage IV than in stages I, II, and III. The depletion of LOC441461 promoted cell proliferation, cell cycle progression, apoptosis, cell motility, and invasiveness. LOC441461 downregulation increased the epithelial-to-mesenchymal transition, as indicated by increased TRAIL signaling and decreased RUNX1 interactions. The interaction of the transcription factors RELA, IRF1, ESR1, AR, POU5F1, TRIM28, and GATA1 with LOC441461 affected the degree of the malignancy of gastric cancer by modulating gene transcription. The present study identified LOC441461 and seven transcription factors as potential biomarkers and therapeutic targets for the treatment of gastric cancer.
Highlights
Gastric cancer is a common malignancy, with a high mortality rate worldwide, and shows substantial incidence in East Asia, Eastern Europe, and South America [1]
The results showed that the expression of LOC441461 correlated negatively with the drug sensitivity of gastric cancer (Figure 4A); whereas, DMSO treatment decreased the rate of apoptosis of LOC441461 knockdown cells (Figure 4A,B)
We suggest that LOC441461 modulates gene transcription, inducing the malignancy of gastric cancer by interacting with RELA, IRF1, ESR1, androgen receptor (AR), POU5F1, Tripartite motif-containing 28 (TRIM28), and GATA1
Summary
Gastric cancer is a common malignancy, with a high mortality rate worldwide, and shows substantial incidence in East Asia, Eastern Europe, and South America [1]. H. pylori infection is the most prevalent, infecting more than 50% of all gastric cancers [2]. Common symptoms of gastric cancer include indigestion, anorexia, weight loss, and abdominal pain [1]. Gastric cancer with the persistence of symptoms before diagnosis can be incurable or in an advanced stage [1]. The diagnosis of gastric cancer is determined using the tumor, node, and metastasis (TNM) classification system, according to the American Joint Committee on Cancer [3]. Clinical staging is determined according to physical examination, biopsy, radiological imaging, and the results of an endoscopy [4–6]. The clinical and pathological staging of gastric cancer is determined by various combinations of the T, N, and M categories [7,8]. For the most advanced gastric cancer, a fluoropyrimidine chemotherapy and platinum-based doublet are typically the backbone regimen [9,10]
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