Research Paper Volume 13, Issue 10 pp 14065—14077

TCF-3-mediated transcription of lncRNA HNF1A-AS1 targeting oncostatin M expression inhibits epithelial-mesenchymal transition via TGFβ signaling in gastroenteropancreatic neuroendocrine neoplasms

Jingwen Xue1, *, , Jianan Bai1, *, , Qin Long1, , Yaling Wei2, , Jialing Pan1, , Xiaolin Li1, , Qiyun Tang1, ,

  • 1 Department of Geriatric Gastroenterology, Jiangsu People’s Hospital, Nanjing Medical University, Nanjing, China
  • 2 Department of Gastroenterology, Shaoxing Central Hospital, Shaoxing, China
* Equal contribution

Received: December 11, 2020       Accepted: March 3, 2021       Published: May 25, 2021
How to Cite

Copyright: © 2021 Xue et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


GEP-NENs: gastroenteropancreatic neuroendocrine neoplasms; lncRNAs: long noncoding RNAs; EMT: epithelial mesenchymal transition; TCF3: transcription factor 3; siRNAs: small interfering RNAs; mTOR: mammalian target of rapamycin; TGF-β: transforming growth factor-β; OSM: oncostatin M; STAT3: signal transducers and activators of transcription 3; SMAD3: Sekelsky mothers against dpp Homolog 3.