LncRNA CERS6-AS1 promotes proliferation and metastasis through the upregulation of YWHAG and activation of ERK signaling in pancreatic cancer

Abstract LncRNAs play essential regulatory roles in pancreatic cancer (PC) tumorigenesis and progression. We aimed to investigate the role of lncRNA CERS6-AS1 in PC. CERS6-AS1 expression was determined in PC tissues and cell lines by PCR analysis. The roles of CERS6-AS1 on proliferation, migration,...

Full description

Bibliographic Details
Main Authors: Jian Xu, Jie Wang, Zhiwei He, Peng Chen, Xueyi Jiang, Yankun Chen, Xinyuan Liu, Jianxin Jiang
Format: Article
Language:English
Published: Nature Publishing Group 2021-06-01
Series:Cell Death and Disease
Online Access:https://doi.org/10.1038/s41419-021-03921-3
id doaj-202ce018cb604ea6bf613a576221d878
record_format Article
spelling doaj-202ce018cb604ea6bf613a576221d8782021-06-27T11:05:06ZengNature Publishing GroupCell Death and Disease2041-48892021-06-0112711310.1038/s41419-021-03921-3LncRNA CERS6-AS1 promotes proliferation and metastasis through the upregulation of YWHAG and activation of ERK signaling in pancreatic cancerJian Xu0Jie Wang1Zhiwei He2Peng Chen3Xueyi Jiang4Yankun Chen5Xinyuan Liu6Jianxin Jiang7Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan UniversityDepartment of Hepatobiliary Surgery, Renmin Hospital of Wuhan UniversityDepartment of Hepatobiliary Surgery, Renmin Hospital of Wuhan UniversityDepartment of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of Guizhou Medical UniversityDepartment of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of Guizhou Medical UniversityDepartment of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of Guizhou Medical UniversityDepartment of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of Guizhou Medical UniversityDepartment of Hepatobiliary Surgery, Renmin Hospital of Wuhan UniversityAbstract LncRNAs play essential regulatory roles in pancreatic cancer (PC) tumorigenesis and progression. We aimed to investigate the role of lncRNA CERS6-AS1 in PC. CERS6-AS1 expression was determined in PC tissues and cell lines by PCR analysis. The roles of CERS6-AS1 on proliferation, migration, invasion, and epithelial to mesenchymal transition (EMT) were confirmed via CCK-8 assay, EDU assay, transwell assay, wound healing assay, and western blot assay. Besides, the interaction between CERS6-AS1 and their target genes was verified by luciferase report assays and RIP assays. Animal assays and clinical data analysis were performed to validate the functions in vivo. We found that lncRNA CERS6-AS1 was highly expressed in PC tissues and cells. Additionally, high expression of CERS6-AS1 was obviously associated with poor prognosis. Functional assays demonstrated that CERS6-AS1 downregulation significantly inhibited PC cell growth and migration. Moreover, CERS6-AS1 exerted as a molecular sponge for miR-217-5p (miR-217), and miR-217 was confirmed as a potential target of CERS6-AS1. Subsequently, miR-217 suppressed PC cell proliferation and metastasis by directly targeting YWHAG, which interacted with RAF1 and promoted its phosphorylation, leading to RAF1-mediated ERK signaling activation and translocation of phosphorylated ERK from the cytoplasm to the nucleus. Mechanically, CERS6-AS1 silencing significantly inhibited PC cell proliferation and metastasis via a miR-217/YWHAG/RAF1 signaling axis. CERS6-AS1 exerts as a carcinogen in PC to promote malignant features and behaves as a competitive endogenous RNA for miR-217. We identified CERS6-AS1 as a potential biomarker or therapeutic target to improve PC diagnosis and treatment outcomes.https://doi.org/10.1038/s41419-021-03921-3
collection DOAJ
language English
format Article
sources DOAJ
author Jian Xu
Jie Wang
Zhiwei He
Peng Chen
Xueyi Jiang
Yankun Chen
Xinyuan Liu
Jianxin Jiang
spellingShingle Jian Xu
Jie Wang
Zhiwei He
Peng Chen
Xueyi Jiang
Yankun Chen
Xinyuan Liu
Jianxin Jiang
LncRNA CERS6-AS1 promotes proliferation and metastasis through the upregulation of YWHAG and activation of ERK signaling in pancreatic cancer
Cell Death and Disease
author_facet Jian Xu
Jie Wang
Zhiwei He
Peng Chen
Xueyi Jiang
Yankun Chen
Xinyuan Liu
Jianxin Jiang
author_sort Jian Xu
title LncRNA CERS6-AS1 promotes proliferation and metastasis through the upregulation of YWHAG and activation of ERK signaling in pancreatic cancer
title_short LncRNA CERS6-AS1 promotes proliferation and metastasis through the upregulation of YWHAG and activation of ERK signaling in pancreatic cancer
title_full LncRNA CERS6-AS1 promotes proliferation and metastasis through the upregulation of YWHAG and activation of ERK signaling in pancreatic cancer
title_fullStr LncRNA CERS6-AS1 promotes proliferation and metastasis through the upregulation of YWHAG and activation of ERK signaling in pancreatic cancer
title_full_unstemmed LncRNA CERS6-AS1 promotes proliferation and metastasis through the upregulation of YWHAG and activation of ERK signaling in pancreatic cancer
title_sort lncrna cers6-as1 promotes proliferation and metastasis through the upregulation of ywhag and activation of erk signaling in pancreatic cancer
publisher Nature Publishing Group
series Cell Death and Disease
issn 2041-4889
publishDate 2021-06-01
description Abstract LncRNAs play essential regulatory roles in pancreatic cancer (PC) tumorigenesis and progression. We aimed to investigate the role of lncRNA CERS6-AS1 in PC. CERS6-AS1 expression was determined in PC tissues and cell lines by PCR analysis. The roles of CERS6-AS1 on proliferation, migration, invasion, and epithelial to mesenchymal transition (EMT) were confirmed via CCK-8 assay, EDU assay, transwell assay, wound healing assay, and western blot assay. Besides, the interaction between CERS6-AS1 and their target genes was verified by luciferase report assays and RIP assays. Animal assays and clinical data analysis were performed to validate the functions in vivo. We found that lncRNA CERS6-AS1 was highly expressed in PC tissues and cells. Additionally, high expression of CERS6-AS1 was obviously associated with poor prognosis. Functional assays demonstrated that CERS6-AS1 downregulation significantly inhibited PC cell growth and migration. Moreover, CERS6-AS1 exerted as a molecular sponge for miR-217-5p (miR-217), and miR-217 was confirmed as a potential target of CERS6-AS1. Subsequently, miR-217 suppressed PC cell proliferation and metastasis by directly targeting YWHAG, which interacted with RAF1 and promoted its phosphorylation, leading to RAF1-mediated ERK signaling activation and translocation of phosphorylated ERK from the cytoplasm to the nucleus. Mechanically, CERS6-AS1 silencing significantly inhibited PC cell proliferation and metastasis via a miR-217/YWHAG/RAF1 signaling axis. CERS6-AS1 exerts as a carcinogen in PC to promote malignant features and behaves as a competitive endogenous RNA for miR-217. We identified CERS6-AS1 as a potential biomarker or therapeutic target to improve PC diagnosis and treatment outcomes.
url https://doi.org/10.1038/s41419-021-03921-3
work_keys_str_mv AT jianxu lncrnacers6as1promotesproliferationandmetastasisthroughtheupregulationofywhagandactivationoferksignalinginpancreaticcancer
AT jiewang lncrnacers6as1promotesproliferationandmetastasisthroughtheupregulationofywhagandactivationoferksignalinginpancreaticcancer
AT zhiweihe lncrnacers6as1promotesproliferationandmetastasisthroughtheupregulationofywhagandactivationoferksignalinginpancreaticcancer
AT pengchen lncrnacers6as1promotesproliferationandmetastasisthroughtheupregulationofywhagandactivationoferksignalinginpancreaticcancer
AT xueyijiang lncrnacers6as1promotesproliferationandmetastasisthroughtheupregulationofywhagandactivationoferksignalinginpancreaticcancer
AT yankunchen lncrnacers6as1promotesproliferationandmetastasisthroughtheupregulationofywhagandactivationoferksignalinginpancreaticcancer
AT xinyuanliu lncrnacers6as1promotesproliferationandmetastasisthroughtheupregulationofywhagandactivationoferksignalinginpancreaticcancer
AT jianxinjiang lncrnacers6as1promotesproliferationandmetastasisthroughtheupregulationofywhagandactivationoferksignalinginpancreaticcancer
_version_ 1721358224341336064