Long noncoding RNA NEAT1 regulates the miR-124-3p/CTNNB1 axis to affect the biological functions of pancreatic cancer cells
10.7659/j.issn.1005-6947.230365
- VernacularTitle:长链非编码RNA NEAT1调控miR-124-3p/CTNNB1轴对胰腺癌细胞生物学功能的影响
- Author:
Wei CHEN
1
;
Zheng HAN
1
;
Shasha HUANG
1
;
Yishan CAI
1
;
Fang GUO
1
;
Xia TIAN
1
Author Information
1. 湖北省武汉市第三医院 消化内科,湖北 武汉 430060
- Publication Type:Journal Article
- Keywords:
Pancreatic Neoplasms;
RNA,Long Noncoding;
MicroRNAs;
Cell Proliferation;
Neoplasm Invasiveness
- From:
Chinese Journal of General Surgery
2025;34(3):495-505
- CountryChina
- Language:Chinese
-
Abstract:
Background and Aims:Long noncoding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)is an oncogenic lncRNA that promotes the progression of various cancers through the competing endogenous RNA(ceRNA)mechanism.Using the TargetScan database,we previously identified binding sites between NEAT1 and microRNA-124-3p(miR-124-3p),as well as between miR-124-3p and catenin beta-1(CTNNB1).Therefore,this study was conducted to investigate the expression of NEAT1,miR-124-3p,and CTNNB1 in pancreatic cancer and their interactions affecting pancreatic cancer cell functions.Methods:A dual-luciferase reporter assay was used to validate the relationships among NEAT1,miR-124-3p,and CTNNB1.The expression levels of NEAT1 and miR-124-3p,as well as CTNNB1 protein expression,were detected in pancreatic cancer tissues and adjacent normal tissues,as well as in pancreatic cancer PANC-1 cells and normal pancreatic epithelial H6C7 cells.PANC-1 cells were transfected with NEAT1 siRNA alone or co-transfected with a miR-124-3p inhibitor.After transfection,changes in PANC-1 cell biological functions,epithelial-mesenchymal transition related protein expression,and tumor growth ability in mice were assessed.Results:The dual-luciferase reporter assay confirmed the targeting relationships between NEAT1 and miR-124-3p,as well as between miR-124-3p and CTNNB1.NEAT1 and CTNNB1 expression levels were significantly upregulated,while miR-124-3p expression was downregulated in pancreatic cancer tissues(vs.adjacent tissues)and in PANC-1 cells(vs.H6C7 cells)(all P<0.05).NEAT1 siRNA transfection led to decreased NEAT1 and CTNNB1 expression and increased miR-124-3p expression in PANC-1 cells.However,co-transfection with a miR-124-3p inhibitor suppressed the expression changes in miR-124-3p and CTNNB1(all P<0.05).NEAT1 siRNA transfection significantly reduced PANC-1 cell proliferation,migration,and invasion,while promoting apoptosis.Additionally,E-cadherin protein expression was upregulated,whereas N-cadherin and vimentin protein expression were downregulated.Tumor growth in mice was also significantly inhibited(all P<0.05).These changes were attenuated upon co-transfection with the miR-124-3p inhibitor(all P<0.05).Conclusion:NEAT1 may act as a ceRNA by competitively binding to miR-124-3p,thereby attenuating miR-124-3p-mediated inhibition of CTNNB1.This leads to CTNNB1 upregulation,ultimately promoting the malignant biological behavior of pancreatic cancer cells.
