miR-125b promotes EMT and metastasis via Wnt/β-catenin signaling pathway in human gastric cancer
- VernacularTitle:miR-125b 通过 Wnt/β-catenin 信号通路促进胃癌细胞上皮间质转化和转移
- Author:
Shuai CHANG
1
;
Yao ZHAO
;
Shunle LI
;
Di ZHANG
;
Li ZHANG
;
Hongjun ZHAI
;
Hong JI
Author Information
- Keywords: gastric cancer; epithelial-mesenchymal transition(EMT); metastasis; miR-125b; Wnt/β-catenin
- From: Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(5):718-725
- CountryChina
- Language:Chinese
- Abstract: Objective To explore the molecular mechanism of miR-125b promoting invasion,metastasis and epithelial-mesenchymal transition(EMT)of gastric cancer cells.Methods The expression of miR-125b in gastric cancer and its adjacent tissues was studied by qRT-PCR.After upregulating or downregulating miR-125b in gastric cancer cells,the protein expressions of DKK3 and SERPINA4 were detected by Western blotting.Dual luciferase reporting assay was used to verify whether miR-125b can target DKK3 and SERPINA4.MKN45 cells were co-transfected with miR-125b inhibitor and target gene siRNA.Migration and invasion experiments were conducted to explore whether miR-125b can regulate the biological function of MKN45 cells through DKK3 and SERPINA4.Then,the regulatory mechanism of SRF on miR-125b was investigated.Finally,by in vivo experiments,the expression of SRF in gastric cancer cells was upregulated or downregulated by lentivirus transfection;the number of lung metastases in nude mice was detected to explore the effect of SRF on gastric cancer cell metastasis.Results In this study,the expression of miR-125b increased in gastric cancer tissues,which was correlated with clinical stage and lymph node metastasis.Dual luciferase reporting experiments showed that DKK3 and SERPINA4 were the direct targets of miR-125b in gastric cancer cells,and could activate the Wnt/β-catenin signaling pathway,thereby promoting the transcription process of EMT-related transcription factors Twist1 and Slug,inducing the occurrence of EMT,and promoting the metastasis of gastric cancer.In vitro and in vivo experiments confirmed that SRF promoted the invasion and metastasis of gastric cancer cells by positively regulating the expression of miR-125b.Conclusion Taken together,SRF/miR-125b axis promotes the EMT and metastasis of gastric cancer cells,and these regulators represent new potential therapeutic targets or biomarkers for gastric cancer.
