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Research Paper Volume 13, Issue 4 pp 6041—6054
Long non-coding RNA CERS6-AS1 facilitates the oncogenicity of pancreatic ductal adenocarcinoma by regulating the microRNA-15a-5p/FGFR1 axis
- 1 Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin, China
- 2 Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin, China
Received: July 20, 2020 Accepted: November 25, 2020 Published: February 13, 2021
https://doi.org/10.18632/aging.202540How to Cite
Copyright: © 2021 Yun 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
The long non-coding RNA CERS6 antisense RNA 1 (CERS6-AS1) has critical regulatory roles in breast cancer progression. Here, we determined CERS6-AS1 expression in pancreatic ductal adenocarcinoma (PDAC) and the roles of CERS6-AS1 in PDAC carcinogenesis. The mechanisms underlying the regulatory actions of CERS6-AS1 in PDAC cells were elucidated in detail. CERS6-AS1 expression was evidently increased in PDAC tissues and cell lines. Patients with PDAC having high CERS6-AS1 expression had shorter overall survival periods than those having low CERS6-AS1 expression. Functionally, the knockdown of CERS6-AS1 attenuated the proliferation, migration, and invasion and stimulated apoptosis of PDAC cells in vitro. Additionally, CERS6-AS1 depletion decreased PDAC tumor growth in vivo. Mechanistically, CERS6-AS1 could competitively bind to microRNA-15a-5p (miR-15a-5p) and effectively work as a molecular sponge in PDAC cells, resulting in the upregulation of fibroblast growth factor receptor 1 (FGFR1), a direct target of miR-15a-5p. Rescue experiments revealed that miR-15a-5p downregulation or FGFR1 restoration rescued the effects of CERS6-AS1 knockdown on the behaviors of PDAC cells. In conclusion, CERS6-AS1 promoted the oncogenicity of PDAC by serving as a competing endogenous RNA to sequester miR-15a-5p and increase FGFR1 expression, which highlights the potential of the CERS6-AS1/miR-15a-5p/FGFR1 pathway as an effective target for cancer therapy.