The function and mechanism of long non-coding RNA FGD5-AS1 in regulating the miR-142-3p/PDK1 signaling axis in gastric cancer
10.7659/j.issn.1005-6947.240537
- VernacularTitle:长链非编码RNA FGD5-AS1调控miR-142-3p/PDK1信号轴在胃癌中的作用及机制
- Author:
Huazhi LI
1
;
Haitao SUN
1
;
Guang CAO
1
;
Yajing ZHANG
1
Author Information
1. 首都医科大学附属北京安贞医院 普通外科,北京 100029
- Publication Type:Journal Article
- Keywords:
Stomach Neoplasms;
RNA,Long Noncoding;
MicroRNAs;
Pyruvate Dehydrogenase Kinase 1;
Neoplasm Invasiveness
- From:
Chinese Journal of General Surgery
2025;34(6):1209-1218
- CountryChina
- Language:Chinese
-
Abstract:
Background and Aims:Studies have shown that the long non-coding RNA(lncRNA)FGD5-AS1 functions as an oncogene in gastric cancer(GC).Our previous bioinformatics analysis revealed potential binding sites between FGD5-AS1 and microRNA-142-3p(miR-142-3p),as well as between miR-142-3p and pyruvate dehydrogenase kinase 1(PDK1).Therefore,this study aimed to investigate the expression and functional role of the FGD5-AS1/miR-142-3p/PDK1 axis in GC cells.Methods:Dual-luciferase reporter assays were used to verify the targeting relationships between FGD5-AS1 and miR-142-3p,and between miR-142-3p and PDK1.qRT-PCR was conducted to measure the expression levels of FGD5-AS1,miR-142-3p,and PDK1 in GC tissues.A knockdown model of FGD5-AS1(sh-FGD5-AS1)and an miR-142-3p inhibitor were constructed and transfected,alone or in combination,into BGC823 GC cells.Cellular behaviors,including proliferation(CCK8,EdU),apoptosis(flow cytometry),migration,and invasion(Transwell assays),were assessed,along with related protein expression(Western blot).A subcutaneous xenograft model in nude mice was used to evaluate the effect of FGD5-AS1 on tumor growth in vivo.Results:The dual-luciferase assays demonstrated that miR-142-3p mimics significantly reduced the luciferase activity of wild-type(WT)FGD5-AS1 and PDK1 reporters(both P<0.05),but had no effect on mutant(MUT)reporters,confirming a direct binding relationship.Knockdown of FGD5-AS1 led to upregulation of miR-142-3p and downregulation of PDK1 in GC cells,with reduced proliferation,migration,and invasion,and enhanced apoptosis(all P<0.05);these effects were reversed by the miR-142-3p inhibitor.In vivo,FGD5-AS1 knockdown significantly inhibited tumor growth in nude mice and decreased Ki-67 and PDK1 expression in tumor tissues(all P<0.05).Conclusion:FGD5-AS1 may act as a ceRNA that sponges miR-142-3p,thereby relieving its suppression on PDK1,and promoting GC cell proliferation and invasion as well as tumor progression.The FGD5-AS1/miR-142-3p/PDK1 axis plays a critical role in the development of GC and may serve as a potential therapeutic target.
