LncRNA SNHG17 promotes gastric cancer progression by epigenetically silencing of p15 and p57

Abstract

Long noncoding RNAs (lncRNA) are attractive biomarkers and therapeutic targets because of their disease- and stage-restricted expression. Small nucleolar RNA host gene 17 (SNHG17) belongs to a large family of noncoding genes hosting small RNAs, with its expression pattern and biological function not clarified in gastric cancer (GC). Thus, we conducted this study to investigate the functional significance and the underlying mechanisms of SNHG17 in GC progression. Our results showed that SNHG17 expression was upregulated in GC tissues and cells, and its high expression was significantly correlated with increased invasion depth, lymphatic metastasis, and advanced TNM stage. The expression of plasma SNHG17 was also found upregulated in patients with GC compared with healthy controls, with a moderate accuracy for diagnosis of GC (area under the receiver operating characteristic curve = 0.748; 95% CI, 0.666-0.830). Gain- and loss-of-function of SNHG17 revealed that SNHG17 promoted GC cell proliferation, cell cycle progression, invasion, and migration and inhibited apoptosis. Mechanistic investigations showed that SNHG17 was associated with polycomb repressive complex 2 and that this association was required for epigenetic repression of cyclin-dependent protein kinase inhibitors, including p15 and p57, thus contributing to the regulation of GC cell cycle and proliferation. Furthermore, rescue experiments indicated that SNHG17 functioned as an oncogene via activating enhancer of zeste homolog 2 in GC cells. Our study provides a new perspective for SNHG17 acting as a noncoding oncogene in GC tumorigenesis, and it may serve as a novel early diagnostic marker and potential target for the treatment of GC.

Keywords: enhancer of zeste homolog 2 (EZH2); gastric cancer (GC); p15; p57; polycomb repressive complex 2 (PRC2); small nucleolar RNA host gene 17 (SNHG17).