Increasing evidence suggests that long noncoding RNAs act as critical regulators in various malignancies. Small nucleolar RNA host gene 6 (SNHG6) plays a role in the progression of human cancers. The present study aims to investigate the molecular mechanism through which SNHG6 promotes the development of gastric cancer (GC).Main methods:
The expression level of SNHG6 in human serum was examined using reverse transcription and quantitative polymerase chain reaction (qRT-PCR). RNA- fluorescence in situ hybridization (FISH) and Cell nucleus/cytoplasm fraction isolation assay were used to detect the cellular distribution of SNHG6. Senescence-associated β-galactosidase (SA-β-gal) activity assay was performed to detect cell senescence. BALB/c male nude mice were used to establish the xenograft model.Key findings:
We found that SNHG6 was up-regulated in human GC tissues and serum. Knockdown of SNHG6 inhibited GC cell proliferation, induced cellular senescence, and reduced xenograft tumor growth in BALB/c nude mice. Knockdown of SNHG6 stimulated p21 expression and the tumor-suppressive effect of SNHG6 in GC cells was dependent on p21. Furthermore, the activation of the c-Jun N-terminal kinase (JNK) pathway and the decrease in Enhancer of Zeste Homolog 2 (EZH2) expression levels represented two mutually independent mechanisms by which SNHG6 knockdown resulted in the upregulation of p21.Significance:
Our findings show that SNHG6 knockdown inhibits GC development by upregulating p21; this effect is dependent on the activation of the JNK pathway and suppression of EZH2 expression. This study indicates that SNHG6 plays an important role in GC progression via the regulation of 21.