IDDF2019-ABS-0124 Upregulation of the long non-coding RNA LINC00460 promotes gastric cancerprogression by epigenetically silencing P21 via EZH2 and indicates poor outcome

Background Multiple studies have revealed that long non-coding RNAs (lncRNAs) extensively participate in human cancer progression. Recently, we found that LINC00460 was an oncogene in promoting colorectal cancer cell proliferation. However, its role in gastric cancer (GC) remains unclear. Methods LINC00460 expression was detected in 80 GC and matched non-cancerous tissues by quantitative reverse transcription PCR. Gain-and loss-of-function experiments were conducted to investigate the biological functions of LINC00460 both in vitro and in vivo. The mechanism of LINC00460 action was explored through bioinformatics, RNA fluorescence in situ hybridization, chromatin immunoprecipitation assay and RNA immunoprecipitation assay. Results LINC00460 was excessively expressed in GC tissues and correlated with advanced stage, larger tumor size and poorer prognosis in GC patients. Forced LINC00460 expression promotes proliferation, whereas loss of LINC00460 function decreased cell proliferation by blocking of cell cycle in GC cells. Mechanistically, LINC00460 could simultaneously interact with EZH2, a core component of polycomb repressive complex 2, and mediates the trimethylation of H3K27 at the promoter region of p21. In addition, rescue experiments determined that LINC00460 oncogenic function is partly dependent on repressing P21. Conclusions Together, our results suggest that LINC00460, as a regulator of proliferation, may serve as a candidate prognostic biomarker and target for the management of GC.