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Propofol Suppresses Gastric Cancer Progression by Regulating circPDSS1/miR-1324/SOX4 Axis
Leyi Liu1, Ting Dong2, Jun Sheng3
1Department of Anesthesiology, Wuhu Hospital of Traditional Chinese Medicine, Wuhu, 241000, People's Republic of China.
Background:
Propofol is a common intravenous anesthetic that exerts an antitumor role in human cancers. Circular RNAs (circRNAs) play crucial roles in the progression of various cancers. However, the relationship between propofol and circRNA decaprenyl diphosphate synthase subunit 1 (circPDSS1) in gastric cancer (GC) remains unclear.
Methods:
Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assays. Cell migration and invasion were assessed by transwell assay. Cell apoptosis was determined by flow cytometry. All protein levels were detected by Western blot assay. The expression levels of circPDSS1, microRNA-1324 (miR-1324), and SRY-box transcription factor 4 (SOX4) mRNA were determined by quantitative real-time PCR (qRT-PCR). The interaction between miR-1324 and circPDSS1 or SOX4 was confirmed by dual-luciferase reporter and RNA pull-down assays. The mice xenograft model was established to investigate the role of propofol and circPDSS1 in vivo.
Results:
Propofol inhibited cell proliferation, migration and invasion and induced apoptosis in GC cells, which could be reversed by upregulating circPDSS1. MiR-1324 was a target of circPDSS1, and circPDSS1 promoted cell proliferation, migration and invasion and reduced apoptosis in propofol-treated cells by sponging miR-1324. Moreover, SOX4 was a direct target of miR-1324, and miR-1324 exerted anticancer role by targeting SOX4 in propofol-treated cells. CircPDSS1 acted as a sponge of miR-1324 to regulate SOX4 expression. Additionally, circPDSS1 overexpression weakened the anticancer role of propofol in vivo.
Conclusion:
Propofol exerted anticancer role in GC through regulating circPDSS1/miR-1324/SOX4 axis, indicating that propofol might be an effective therapeutic medicine for GC treatment.
Insights
Propofol, an anesthetic, shows anticancer effects in gastric cancer (GC) by regulating the circPDSS1/miR-1324/SOX4 pathway. This suggests propofol
Area of Science:
- Oncology
- Molecular Biology
- Anesthesiology
Background:
- Propofol, a common intravenous anesthetic, exhibits antitumor properties in various human cancers.
- Circular RNAs (circRNAs) are implicated in cancer progression, but their role in gastric cancer (GC) concerning propofol remains unexplored.
- This study investigates the novel relationship between propofol and circRNA decaprenyl diphosphate synthase subunit 1 (circPDSS1) in GC.
Purpose of the Study:
- To elucidate the mechanism by which propofol exerts its antitumor effects in gastric cancer.
- To investigate the role of circPDSS1, miR-1324, and SOX4 in propofol-mediated anticancer activity in GC.
- To explore the potential of propofol as a therapeutic agent for GC treatment.
Main Methods:
- Cell proliferation, migration, invasion, and apoptosis were assessed using CCK-8, colony formation, EdU, and flow cytometry assays.
- Quantitative real-time PCR (qRT-PCR) and Western blot were employed to determine the expression levels of circPDSS1, miR-1324, and SOX4.
- Dual-luciferase reporter and RNA pull-down assays confirmed the interactions between circPDSS1, miR-1324, and SOX4. In vivo efficacy was evaluated using a mice xenograft model.
Main Results:
- Propofol inhibited GC cell proliferation, migration, and invasion while inducing apoptosis; these effects were reversed by upregulating circPDSS1.
- CircPDSS1 acts as a molecular sponge for miR-1324, promoting GC progression and counteracting propofol's effects.
- MiR-1324 directly targets SOX4, mediating the anticancer role of propofol. CircPDSS1 overexpression diminished propofol's in vivo anticancer efficacy.
Conclusions:
- Propofol demonstrates significant anticancer activity in gastric cancer by modulating the circPDSS1/miR-1324/SOX4 molecular axis.
- The findings suggest that propofol holds promise as an effective therapeutic agent for gastric cancer treatment.
- Targeting the circPDSS1/miR-1324/SOX4 pathway could be a viable strategy for enhancing propofol-based GC therapy.
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