LUCAT1 Epigenetically Downregulates the Tumor Suppressor Genes and in Gastric Cancer.

Purpose: The mechanisms of Wnt/β-catenin pathway signaling and abnormal expression of tumor suppressor genes is not well known in gastric cancer (GC). Long non-coding RNA (lncRNA) has recently been identified as a possible link therein. In this study, we investigated the role of lung cancer associated transcript 1 (LUCAT1) in GC.

Materials And Methods: The expression of LUCAT1 in GC cell lines and 100 tissue samples was examined by qRT-PCR. Two different siRNAs were used for knockdown of LUCAT1 expression. Cell viability was assessed by MTT assay. To analyze metastasis, scratch wound-healing assay, a Matrigel invasion assay, and colony formation assay were performed. Apoptosis was analyzed by PI/Annexin-V staining. To check the methylation status in tumor suppressor genes, methylation-specific PCR was carried out. Western blot was performed to detect epithelial-mesenchymal transition and apoptosis markers upon silencing of LUCAT1 (siLUCAT1).

Results: LUCAT1 expression in GC cell lines and tissues was significantly elevated, compared to that in normal gastric cells and adjacent non-tumor tissues (<0.001). Two different siRNAs for LUCAT1 reduced cell proliferation, invasion, and migration, compared to siCT (<0.05), and these reductions were restored by pcDNA-LUCAT1 (<0.05). siLUCAT1 elicited upregulation of the expression of and . The expression of was reduced by siLUCAT1, and this reduction was correlated with methylation of and . Inhibition of LUCAT1 up-regulated EZH2 expression and resulted in demethylation of and through the Wnt/β-catenin signaling pathway.

Conclusion: We concluded that LUCAT1 induces methylation of and , thereby regulating Wnt/β-catenin signaling in GC.