HOXA3-Induced Exosomal lncRNA RNF144A-AS1 Promotes Liver Metastasis of Gastric Cancer via Interacting with PUF60 Protein and Sponging miR-361-3p

Abstract Background: Long non-coding RNA (lncRNA) plays an important regulatory role in the development and progression of gastric cancer(GC). However, the biological role and potential molecular mechanism of lncRNA RNF144A-AS1 in liver metastasis of gastric cancer(GCLM) remain unclear. Methods: LncRNAs associated with GCLM were identified by microarray. Gain or loss of function approaches was used to investigate the biological functions of RNF144A-AS1. The expression of RNF144A-AS1 was detected by real-time quantitative PCR, and the molecular mechanism of RNF144A-AS1 was investigated by RNA pull-down assay, Western blot, luciferase activity, RNA immunoprecipitation. Finally, nude mouse models and bioluminescence imaging were used to verify the role of RNF144A-AS1 in GCLM in vivo. Results:We identified that RNF144A-AS1 was highly expressed in GC by microarray.RNF144A-AS1 was related to GCLM,and poor DFS and OS. The expression of RNF144A-AS1 in serum exosomes of GC patients was significantly increased, while the level of RNF144A-AS1 was significantly decreased after GC resection. Overexpression of RNF144A-AS1 in exosomes can promote the growth and invasion of co-cultured GC cells in vitro. The down-regulation of RNF144A-AS1 induced the proliferation, migration, and invasion of GC cells in vitro and in vivo. Mechanistically, the transcription factor HOXA3 bound to the promoter region of RNF144A-AS1 could activate RNF144A-AS1, and RNF144A-AS1 promotes GCLM via interacting with PUF60 protein and sponging miR-361-3p.Conclusions: The present study indicated that exosome RNF144A-AS1 overexpression contributes to GCLM and would be a promising biomarker for the diagnosis and prognosis of GCLM.