LBX2-AS1/miR-219a-2-3p/FUS/LBX2 positive feedback loop contributes to the proliferation of gastric cancer.

BACKGROUND:Long non-coding RNAs (lncRNAs) are increasingly investigated in numerous carcinomas containing gastric cancer (GC). The aim of our research is to inquire about the expression profile and role of LBX2-AS1 in GC. METHODS:The expressions of LBX2-AS1, miR-219a-2-3p, FUS and LBX2 were measured by qRT-PCR. Western blot evaluated FUS and LBX2 protein levels. Cell proliferation and apoptosis were, respectively, evaluated by CCK-8, colony formation, EdU, flow cytometry and TUNEL assays. FISH and subcellular fractionation assays examined the position of LBX2-AS1. The binding between genes were certified by RIP, RNA pull-down, ChIP and luciferase reporter assays. Pearson correlation analysis analyzed the association of genes. Kaplan-Meier method detected the relationship of LBX2-AS1 expression with overall survival. RESULTS:The up-regulation of LBX2-AS1 in GC tissues and cells was verified. Function assays proved that LBX2-AS1 down-regulation restricted the proliferation ability. Then, we unveiled the LBX2-AS1/miR-219a-2-3p/FUS axis. Additionally, LBX2-AS1 positively regulated LBX2 mRNA stability via FUS. LBX2 transcriptionally modulated LBX2-AS1. In the end, rescue and in vivo experiments validated the whole regulatory mechanism. CONCLUSION:LBX2-AS1/miR-219a-2-3p/FUS/LBX2 positive feedback loop mainly affected the proliferation and apoptosis abilities of GC cells, offering novel therapeutic targets for the treatment of patients with GC.

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