Long Noncoding RNA Acts as a microRNA-574 Sponge Thereby Enhancing the Aggressiveness of Gastric Cancer via HDAC4 Upregulation.

PURPOSE

The long noncoding RNA plays an important part in the genesis and progression of multiple human cancers. Nonetheless, little is known regarding its expression, roles, and mechanisms of action in gastric cancer (GC). This study was aimed at investigating the relationship between and GC and illustrating the mechanisms of action of therein.

METHODS

expression in GC was measured via reverse-transcription quantitative PCR. A series of experiments including Cell Counting Kit-8 assay, flow-cytometric analysis of apoptosis, Transwell migration and invasion assays, and in vivo tumorigenesis experiment were conducted to test the effects of on the malignant phenotype of GC cells. The molecular events behind the oncogenic actions of in GC were elucidated through subcellular fractionation, RNA immunoprecipitation assay, bioinformatics analysis and luciferase reporter assay.

RESULTS

upregulation was confirmed in GC tissues and cell lines. Higher expression was associated with adverse clinical parameters and negatively correlated with patient overall survival. knockdown inhibited GC cell proliferation, facilitated apoptosis, and reduced migration and invasion in vitro. Further experiments revealed that knockdown decreased the tumor growth of GC cells in vivo. Mechanistically, functioned as a competing endogenous RNA upregulating histone deacetylase 4 (HDAC4) by sponging microRNA-574 (miR-574). Rescue experiments indicated that miR-574 inhibition and HDAC4 reintroduction reversed the effects of the knockdown on GC cells.

CONCLUSION

The -miR-574-HDAC4 regulatory network contributes to the malignancy of GC, thereby offering a novel target for the diagnosis, prognosis, and/or treatment of GC.