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
- 1 Department of Geriatric Gastroenterology, Jiangsu People’s Hospital, Nanjing Medical University, Nanjing, China
- 2 Department of Gastroenterology, Shaoxing Central Hospital, Shaoxing, China
Received: December 11, 2020 Accepted: March 3, 2021 Published: May 25, 2021
https://doi.org/10.18632/aging.203024How 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.
Abstract
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.
Abbreviations
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.