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Sevoflurane Suppresses Colon Cancer Cell Malignancy by Regulating circ-PI4KA
Suqing Sun1, Peng Wang1, Lijie Ren1
1Department of Anesthesia, Tianjin Fifth Central Hospital, Tianjin, People's Republic of China.
Purpose:
To explore the effect of SEV on colon cancer cells through circ-PI4KA.
Methods:
The RNA level of circular RNA_0062389, microRNA-331-3p and LIM and SH3 protein 1 was determined by quantitative real-time polymerase chain reaction. Protein expression was detected by Western blot. Cell proliferation was investigated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide, cell colony formation and 5-ethynyl-29-deoxyuridine assays. Cell apoptosis was demonstrated using Annexin V-fluorescein isothiocyanate/propidium iodide double staining assay. Cell migration and invasion were detected by transwell assay. The target relationship between miR-331-3p and circ-PI4KA or LASP1 was predicted by starBase v2.0 online database, and identified by a dual-luciferase reporter assay. The effects between SEV treatment and circ-PI4KA knockdown on tumor formation were presented by in vivo tumor formation assay.
Results:
Circ-PI4KA and LASP1 expressions were dramatically upregulated, while miR-331-3p was downregulated in colon cancer tissues and cells, respectively. SEV exposure significantly decreased the expression of circ-PI4KA and LASP1, but increased miR-331-3p expression. SEV inhibited cell proliferation, migration and invasion, and induced cell apoptosis by regulating circ-PI4KA. Furthermore, circ-PI4KA interacted with miR-331-3p, and miR-331-3p interacted with LASP1. SEV inhibited tumor growth by controlling circ-PI4KA in vivo.
Conclusion:
Circ-PI4KA attenuated SEV-treated colon cancer cell malignancy by upregulating LASP1 through binding to miR-331-3p, which provided a new mechanism for studying surgery-mediated therapy of colon cancer.
Insights
Sevoflurane (SEV) impacts colon cancer by downregulating circ-PI4KA, which increases miR-331-3p and inhibits LASP1. This mechanism reduces cancer cell malignancy and tumor growth.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Colon cancer is a significant global health concern.
- Circular RNAs (circRNAs) play crucial roles in various cancers, including colon cancer.
- Sevoflurane (SEV), an anesthetic, has shown potential anti-cancer properties.
Purpose of the Study:
- To investigate the effect of SEV on colon cancer cells.
- To elucidate the role of circ-PI4KA in SEV-mediated anti-cancer activity.
- To explore the molecular mechanism involving circ-PI4KA, miR-331-3p, and LASP1.
Main Methods:
- Quantitative real-time PCR and Western blot to assess RNA and protein expression.
- Cell proliferation, apoptosis, migration, and invasion assays to evaluate cellular functions.
- Dual-luciferase reporter assays to confirm molecular interactions.
- In vivo tumor formation assays to assess anti-cancer effects in a living organism.
Main Results:
- Circ-PI4KA and LASP1 were upregulated, while miR-331-3p was downregulated in colon cancer.
- SEV treatment decreased circ-PI4KA and LASP1 expression and increased miR-331-3p expression.
- SEV inhibited colon cancer cell proliferation, migration, and invasion, and induced apoptosis by regulating circ-PI4KA.
- Circ-PI4KA directly binds to miR-331-3p, which in turn targets LASP1.
- SEV inhibited tumor growth in vivo by modulating the circ-PI4KA pathway.
Conclusions:
- Circ-PI4KA acts as a sponge for miR-331-3p, leading to increased LASP1 expression and promoting colon cancer malignancy.
- SEV attenuates colon cancer cell malignancy by downregulating circ-PI4KA, thereby upregulating miR-331-3p and inhibiting LASP1.
- This study reveals a novel mechanism for SEV's anti-cancer effects and provides insights into surgery-mediated cancer therapy.
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