Long noncoding RNAs play key roles in several cancers, but their potential functions in gastroenteropancreatic neuroendocrine neoplasms remain to be investigated. We performed GeneChip assay to explore differentiated lncRNAs in gastric NENs and peri-cancerous tissues. The regulation of HNF1A-AS1 on biological behavior of GEP-NENs cells and in vivo xenograft model was confirmed by CCK8, colony formation assay, transwell, western blot and qRT-PCR. We next detected the potential transcription factors and the binding sites between them with bioinformatic analysis. qRT-PCR was performed to analyze the exact relationship between them. HNF1A-AS1 expression was decreased in gastric NENs tissues (p < 0.01). Over-expression of HNF1A-AS1 suppressed cellular proliferation, migration and invasion. Knockdown of transcription factor 3 inhibited the expression of HNF1A-AS1 and promoted cellular migration and invasion. Oncostatin M was identified as the downstream target of HNF1A-AS1. Inhibition of transforming growth factor-β activity inhibited HNF1A-AS1/Oncostatin M-mediated epithelial-mesenchymal transition. Our data suggest that transcription factor 3/HNF1A-AS1/Oncostatin M axis inhibits the tumorigenesis and metastasis of gastroenteropancreatic neuroendocrine neoplasms via transforming growth factor-β signaling.
Keywords: TGFβ signaling; gastroenteropancreatic neuroendocrine neoplasms; lncRNA HNF1A-AS1; oncostatin M; transcription factor 3.