Long noncoding RNA SPRY4-IT1 predicts poor patient prognosis and promotes tumorigenesis in gastric cancer.

Abstract

Gastric cancer (GC) is the second common cause of cancer-related death worldwide. Long noncoding RNAs (lncRNAs) are emerging as novel regulators in the cancer paradigm. However, investigation of lncRNAs on GC is still in its infancy. In this study, we focused on lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) and investigated its expression pattern, clinical significance, biological function, and molecular mechanism in GC. SPRY4-IT1 expression was examined, and its correlation with clinicopathological characteristics and patient prognosis was analyzed. A series of assays were performed to understand the role of SPRY4-IT1 in GC. SPRY4-IT1 expression was elevated in GC tissues and cell lines, and SPRY4-IT1 levels were highly positively correlated with tumor size, invasion depth, distant metastasis, TNM stage, and reduced overall survival (OS) and disease-free survival (DFS). A multivariate analysis showed that SPRY4-IT1 expression is an independent prognostic factor of OS and DFS in patients with GC. Additionally, the results of in vitro assays showed that the suppression of SPRY4-IT1 expression in GC cell line MKN-45 significantly reduced cell proliferation, colony formation, and cell migration/invasion. Moreover, the tumorigenic effects of SPRY4-IT1 were partially mediated by the regulation of certain cyclins and matrix metalloproteinases (MMPs)-related genes. Our data suggest that SPRY4-IT1 plays a critical role in GC tumorigenesis and may represent a novel prognostic marker and potential therapeutic target in patients with GC.