ESM1 suppresses LncRNA GAS5/miR-23a-3p/PTEN axis to promote the cisplatin-chemotherapy resistance of ovarian cancer cells via activating the PI3K/AKT pathway
Abstract Background Cisplatin chemotherapy is an important treatment for advanced ovarian cancer (OC). However, the development of cisplatin resistance greatly limits the survival time of OC patients. Endothelial cell-specific molecule 1 (ESM1) has been found to be an important proto-oncogene promot...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-03-01
|
| Series: | Discover Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s12672-025-02113-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Abstract Background Cisplatin chemotherapy is an important treatment for advanced ovarian cancer (OC). However, the development of cisplatin resistance greatly limits the survival time of OC patients. Endothelial cell-specific molecule 1 (ESM1) has been found to be an important proto-oncogene promoting OC, but its mediating OC cisplatin resistance remains unknown. Methods We used quantitative polymerase chain reaction (qPCR) to measure transcription levels of ESM1, Growth arrest specific transcript 5 (GAS5), miR-23a-3p, and Phosphatase And Tensin Homolog (PTEN). A double luciferase reporter gene assay confirmed the direct binding of GAS5 to miR-23a-3p and miR-23a-3p to PTEN mRNA. The effects of ESM1, GAS5, miR-23a-3p, and PTEN on OC cisplatin resistance were tested with an Half Maximal Inhibitory Concentration (IC50) assay. Flow cytometry was used to assess the effects of ESM1, GAS5, and miR-23a-3p on cisplatin-induced OC apoptosis. Changes in apoptosis-related proteins and PI3K/AKT-related proteins were analyzed with western blot (WB). Results ESM1 inhibits the levels of GAS5 and PTEN but increases miR-23a-3p. ESM1 and miR-23a-3p promote OC cisplatin resistance. GAS5 and miR-23a-3p promote cisplatin sensitivity for OC cells. Moreover, the main molecular mechanism is the ESM1/GAS5/miR-23a-3p/PTEN/PI3K/Akt signaling axis. Conclusion ESM1 promotes OC cisplatin resistance by activating the Phosphoinositide-3-Kinase (PI3K)/AKT Serine/Threonine Kinase (Akt) signaling pathway through the GAS5/miR-23a-3p/PTEN signaling axis. This suggests that prescriptive ESM1 regulates key downstream molecular mechanisms via non-coding RNA and can be used before neoadjuvant chemotherapy in OC is initiated. |
|---|---|
| ISSN: | 2730-6011 |