Propofol suppresses gastric cancer tumorigenesis by modulating the circular RNA‑PVT1/miR‑195‑5p/E26 oncogene homolog 1 axis

Sui,Hongyang; Zhu,Changju; Li,Zhenzhen; Yang,Jianjun

doi:10.3892/or.2020.7725

Propofol suppresses gastric cancer tumorigenesis by modulating the circular RNA‑PVT1/miR‑195‑5p/E26 oncogene homolog 1 axis

Authors:
- Hongyang Sui
- Changju Zhu
- Zhenzhen Li
- Jianjun Yang
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Affiliations: Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Medical Biology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: August 10, 2020 https://doi.org/10.3892/or.2020.7725
Pages: 1736-1746

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Abstract

Propofol is frequently used for anesthesia in cancer surgery. It has been suggested that treatment with propofol serves a tumor‑suppressing role in human gastric cancer (GC). Therefore, the present study aimed to explore the potential mechanism of propofol in GC. In the present study, GC cell lines (HGC‑27 and AGS) were treated with various concentrations of propofol, and an MTT assay was performed to detect the cell viability. In addition, flow cytometry and Transwell assays were used to evaluate the apoptosis and invasive ability of GC cells, respectively. Western blotting was performed to detect the protein levels of cyclin‑dependent kinase inhibitor P21 (P21), B‑cell lymphoma‑2 (Bcl‑2), matrix metalloproteinase 9 (MMP9) and E26 oncogene homolog 1 (ETS1). Furthermore, reverse transcription‑quantitative PCR was used to examine the expression levels of circular RNA‑PVT1 (circ‑PVT1), micoRNA‑195‑5p (miR‑195‑5p) and ETS1 in GC tissues and cells. The target interaction between miR‑195‑5p and circ‑PVT1 or ETS1 was predicted through bioinformatics analysis, and verified by dual‑luciferase reporter gene assay. In addition, a mouse xenograft model was established for in vivo experiments. It was identified that propofol inhibited the viability and invasion, but promoted apoptosis of HGC‑27 and AGS cells in a dose‑dependent manner. Propofol could inhibit Bcl‑2 and MMP9 expression, and increase P21 expression in GC cells. The expression levels of circ‑PVT1 and ETS1 were increased in GC tissues and cells, and miR‑195‑5p was decreased. Additionally, the treatment with propofol could lead to decreased circ‑PVT1 expression in GC cells. These results could be reversed by ETS1 upregulation or miR‑195‑5p‑knockdown in GC cells. Furthermore, circ‑PVT1 could act as a miR‑195‑5p sponge to modulate ETS1 expression. Additionally, the effects of transfection with circ‑PVT1 small interfering RNA (si‑circ‑PVT1) on HGC‑27 and AGS cells could be reversed by treatment with miR‑195‑5p inhibitor. Meanwhile, miR‑195‑5p inhibitor reversed the si‑circ‑PVT1‑induced low expression of ETS1. Downregulation of ETS1 induced by propofol in HGC‑27 and AGS cells could be restored by circ‑PVT1 upregulation or miR‑195‑5p silencing. Circ‑PVT1 silencing facilitated the propofol‑induced anti‑GC effect in vivo. In conclusion, the present study indicated that propofol inhibited the proliferation and invasion, but enhanced the apoptosis of GC cells by regulating the circ‑PVT1/miR‑195‑5p/ETS1 axis.

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