Abstract

Gastric cancer (GC) is among the most frequently occurring malignancies worldwide. In recent years, long noncoding RNAs (lncRNAs) have been widely studied because of their ability to regulate the cellular processes involved with tumorigenesis. The present study aims to investigate the underlying molecular mechanism by which lncRNA urothelial carcinoma-associated 1 (UCA1) influences the progression of GC. Differentially expressed lncRNA UCA1 was initially identified by microarray-based analysis, after which a high expression of UCA1 was determined in GC tissues and cells. It is important to note that UCA1 could upregulate the expression of phosphatase of regenerating liver-3 (PRL-3) by sponging miR-495. The expression of UCA1 and miR-495 was altered in human GC cells to evaluate cell activity in vitro, as well as peritoneal metastasis and tumor formation ability in vivo. Results suggested that increased expression of UCA1 promoted cell proliferation, migration, and invasion, accompanied by suppressed cell apoptosis, as well as enhanced peritoneal metastasis and tumorigenesis of GC cells. Meanwhile, the upregulated expression of miR-495 could reverse the promotive effects exerted by UCA1. Taken conjointly, UCA1, as a competing endogenous RNA (ceRNA) of miR-495, could accelerate the development of GC by upregulating PRL-3, highlighting a potentially promising basis for the targeted intervention treatment of GC.

Highlights

  • Gastric cancer (GC) is a severe public health burden, leading to over 723,000 deaths worldwide on an annual basis.[1,2] The incidence of GC follows a wide geographical variation, where Asian countries including China, Japan, and Korea exhibit the highest incidence rate of GC in comparison with the rest of the world.[3]

  • urothelial carcinoma-associated 1 (UCA1) Was Highly Expressed in GC Tissues and Cell Lines GC-related microarray expression data (GEO): GSE65801 and GSE103236 microarray data showed that UCA1 was upregulated in GC (Figures 1A and 1B). qRT-PCR results indicated that the relative expression of UCA1 was higher in GC tissues than that of their comparative adjacent normal tissues (Figure 1C), with higher expression recorded in GC cells (MKN-28, MKN-45, SGC-7901, BGC-823, and MGC-803) than in normal gastric epithelial cells (GSE-1) (Figure 1D)

  • 25μm with log rank test was used to analyze the relationship between UCA1 expression and GC patient survival, and the results showed that GC patients with low expression of UCA1 were observed with prolonged survival (p < 0.05) (Figure 1E)

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Summary

Introduction

Gastric cancer (GC) is a severe public health burden, leading to over 723,000 deaths worldwide on an annual basis.[1,2] The incidence of GC follows a wide geographical variation, where Asian countries including China, Japan, and Korea exhibit the highest incidence rate of GC in comparison with the rest of the world.[3]. The prognosis and survival of advanced GC remain poor.[6] Tumor invasion and metastasis are two crucial factors contributing to poor prognosis in patients suffering from cancer. Almost 80% of GC recurrences present as peritoneal metastasis, with the underlying mechanism continuing to elude researchers and clinicians alike.[7] Recent studies have uncovered promising possible cellular targets for drug treatment; current molecular biology and advanced treatment options of GC still require further analysis and better understanding.[8,9,10]

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