Research Paper Volume 13, Issue 14 pp 18924—18945
MicroRNA-1252-5p, regulated by Myb, inhibits invasion and epithelial-mesenchymal transition of pancreatic cancer cells by targeting NEDD9
- 1 Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, China
- 2 Department of Hepatobiliary Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, China
- 3 Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, China
Received: December 14, 2020 Accepted: May 23, 2021 Published: July 27, 2021
https://doi.org/10.18632/aging.203344How 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
MicroRNAs (miRNAs) are known to be involved in the development and progression of pancreatic cancer (PAC). The expression levels and roles of miR-1252-5p in PAC remain unclear. Quantitative real-time PCR and in situ hybridization were used to detect miR-1252-5p expression in PAC cells and human tissues. We studied the gain and loss of function of miR-1252-5p in the PAC cell lines in vitro and in vivo. The direct targets of miR-1252-5p were analyzed using public databases and a dual-luciferase reporter assay. Expression levels of miR-1252-5p are downregulated in PAC cell lines and tissue samples, and its expression is negatively associated with adverse clinical features and poor prognosis. In vitro and in vivo experiments show that miR-1252-5p overexpression inhibits the proliferation, migration, invasion, and epithelial-mesenchymal transition of PAC cells, and miR-1252-5p knockdown enhances these biological behaviors. MiR-1252-5p negatively regulates neural precursor cell expressed, developmentally downregulated 9 (NEDD9) by directly binding its 3'- untranslated region. Further mechanism research revealed that the SRC/STAT3 pathway is involved in miR-1252-5p/NEDD9 mediation of PAC's biological behaviors. We also verified that Myb inhibited miR-1252-5p by directly binding at its promoter. MiR-1252-5p may act as a tumor-suppressing miRNA in PAC and may be a potential therapeutic target for PAC patients.