Long non-coding RNA HNF1A-AS1 upregulates OTX1 to enhance angiogenesis in colon cancer via the binding of transcription factor PBX3

Colon cancer shows characteristics of metastasis, which is associated with angiogenesis. Increasing evidence highlights long non-coding RNAs (lncRNAs) as important participants in angiogenesis of cancers, including colon cancer. Hence, this study investigated the role of HNF1A-AS1 in angiogenesis of colon cancer. RT-qPCR and Western blot analysis were applied to detect HNF1A-AS1 and OTX1 expression in colon cancer tissues and cell lines. Then the interactions among HNF1A-AS1, PBX3, OTX1 and ERK/MAPK pathway were evaluated with RNA pull-down, RIP, ChIP and dual-luciferase reporter gene assays. Next, HCT116 and SW620 cells were treated with si-HNF1A-AS1 and/or oe-OTX1 plasmids to assess the effects of HNF1A-AS1 and OTX1 on angiogenesis, which was further evaluated in nude mice injected with SW620 cells transfected with sh-HNF1A-AS1 or sh-OTX1 lentivirus. HNF1A-AS1 and OTX1 were highly expressed in colon cancer. Silencing of HNF1A-AS1 inhibited angiogenesis of colon cancer in vivo and in vitro. HNF1A-AS1 increased the OTX1 expression by binding to transcription factor PBX3 to promote angiogenesis in colon cancer. Further, HNF1A-AS1 upregulated OTX1 to activate the ERK/MAPK pathway. Altogether, our findings identified HNF1A-AS1 as a tumor-promoting RNA in colon cancer, which could serve as a potential therapeutic target for colon cancer treatment.