Molecular mechanisms of TPT1-AS1 in regulating epithelial ovarian cancer cell invasion, migration, and angiogenesis by targeting the miR-324/TWIST1 axis.
- Author:
Aiping WANG
1
;
Yingying QI
2
,
3
Author Information
1. Department of Gynecology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, China.
2. Department of Gynecology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, China. *Corresponding author, E-mail: yingyingqi1234@
3. com.
- Publication Type:Journal Article
- MeSH:
Humans;
MicroRNAs/metabolism*;
Female;
Cell Movement/genetics*;
Ovarian Neoplasms/blood supply*;
Twist-Related Protein 1/metabolism*;
Cell Line, Tumor;
Neovascularization, Pathologic/genetics*;
Neoplasm Invasiveness;
Carcinoma, Ovarian Epithelial/metabolism*;
Nuclear Proteins/metabolism*;
Cell Proliferation/genetics*;
Epithelial-Mesenchymal Transition/genetics*;
Gene Expression Regulation, Neoplastic;
RNA, Long Noncoding/metabolism*;
Cadherins/genetics*;
Vascular Endothelial Growth Factor A/genetics*;
Vimentin/genetics*;
Angiogenesis
- From:
Chinese Journal of Cellular and Molecular Immunology
2025;41(6):536-543
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism of TPT1-AS1 targeting miR-324/TWIST1 axis to regulate the proliferation, invasion, migration and angiogenesis of epithelial ovarian cancer (EOC) cells, thereby affecting ovarian cancer (OC) progression. Methods RT-qPCR was used to detect the expression of TPT1-AS1 and miR-324 in 29 OC lesions and adjacent tissue samples. The two OC cell models of TPT1-AS1 overexpression and miRNA324 knockdown were constructed, and the cell proliferation, invasion and migration abilities were detected by CCK-8, TranswellTM and scratch test. Western blot analysis was used to detect the protein expression levels of TWIST1, epithelial cadherin (E-cadherin), Vimentin, and vascular endothelial growth factor A (VEGF-A) in OC cells. Fluorescence in situ hybridization (FISH) and RNA pull-down experiments were used to verify the interaction between TPT1-AS1 and miR-324. Immunohistochemistry and Targetscan bioinformatics analysis were used to verify the negative regulatory role of miR-324 in the epithelial-mesenchymal transition (EMT) process. Results The TPT1-AS1 expression was significantly higher in OC tissues than that in para-cancerous tissues, while the miR-324 expression was significantly lower. In SKOV3 cells with TPT1-AS1 overexpression, the miR-324 expression decreased significantly, and TPT1-AS1 was negatively correlated with miR-324. It was also found that TPT1-AS1 and miR-324 were co-expressed in OC cells, and there was a direct binding relationship between them. Down-regulation of miR-324 significantly promoted the proliferation, invasion and migration of SKOV3 cells. Further studies revealed that miR-324 had a binding site at the 3'-UTR end of the TWIST1, a key transcription factor for EMT. Inhibiting miR-324 expression increased the transcription level of TWIST1, leading to a decrease in E-cadherin protein expression and an increase in Vimentin protein expression. Additionally, the downregulation of miR-324 resulted in an increased expression level of VEGF-A protein, which in turn enhanced angiogenesis of OC. Conclusion TPT1-AS1 promotes EOC cell proliferation, invasion, migration and angiogenesis by negatively regulating the miR-324/TWIST1 axis, thus promoting the development of OC. These findings provide new potential targets for the diagnosis and treatment of OC.
