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Published on: October 4, 2019
Propofol inhibits glioma progression by regulating circMAPK4/miR-622/HOXA9 axis
Gaopeng Xiao1, Liuqiong Yu2, Wenmin Tan3
1Department of Anesthesiology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, 157 Jin Bi Road, Xishan District, Kunming, 650000, Yunnan, China.
Abstract:
Propofol has a tumor-suppressive role in glioma, but the mechanism by which propofol is involved in glioma progression is largely unknown. This study aims to explore a potential circular RNAs (circRNAs)/microRNAs (miRNAs)/mRNA network in response to Propofol in glioma. Human glioma cell lines (U251 and LN229) were suffered from Propofol treatment (5 μg/mL for 24 h) and transfection. circRNA mitogen-activated protein kinase 4 (circMAPK4), miR-622, homeobox A9 (HOXA9) abundances were determined by quantitative reverse transcription polymerase chain reaction and western blot. Migration and invasion were analyzed via transwell analysis. Cell proliferation was evaluated using Cell Counting Kit-8 and colony formation analysis. Cell apoptosis and related protein expression were determined via flow cytometry and western blot. Target relationship was assessed via dual-luciferase reporter analysis, RNA pull-down and RNA immunoprecipitation. Propofol reduced circMAPK4 expression. Propofol inhibited cell proliferation, migration and invasion, while increased apoptosis via decreasing circMAPK4 in glioma cells. miR-622 was targeted via circMAPK4. circMAPK4 knockdown decreased glioma cell growth, migration and invasion by up-regulating miR-622. miR-622 knockdown reversed the effect of Propofol on glioma progression. HOXA9 was targeted by miR-622, and its expression was decreased by Propofol treatment. miR-622 overexpression restrained glioma progression via decreasing HOXA9. Propofol regulated circMAPK4/miR-622/HOXA9 axis in glioma cells. Propofol constrains glioma progression by regulating circMAPK4/miR-622/HOXA9 axis in vitro. Propofol restrains glioma cell growth, migration and invasion. circMAPK4 can regulate HOXA9 by sponging miR-622 in glioma cells. Propofol represses glioma progression via a circMAPK4/miR-622/HOXA9 axis.
Insights
Propofol inhibits glioma progression by regulating the circMAPK4/miR-622/HOXA9 pathway. This mechanism involves propofol reducing circMAPK4, which in turn affects miR-622 and HOXA9 expression, ultimately suppressing tumor growth.
Area of Science:
- Oncology
- Molecular Biology
- Neuroscience
Background:
- Propofol exhibits tumor-suppressive properties in glioma.
- The precise molecular mechanisms underlying propofol's effects on glioma progression remain largely unelucidated.
Purpose of the Study:
- To investigate the potential role of a circular RNA (circRNA)/microRNA (miRNA)/mRNA network in mediating propofol's effects on glioma.
- To explore the circMAPK4/miR-622/HOXA9 axis in propofol-treated glioma cells.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction and western blot were used to determine the expression levels of circMAPK4, miR-622, and HOXA9.
- Cell proliferation, migration, invasion, and apoptosis assays (Cell Counting Kit-8, colony formation, transwell, flow cytometry) were performed.
- Dual-luciferase reporter assays, RNA pull-down, and RNA immunoprecipitation were employed to validate target relationships.
Main Results:
- Propofol treatment reduced circMAPK4 expression and inhibited glioma cell proliferation, migration, and invasion, while enhancing apoptosis.
- circMAPK4 was found to target and downregulate miR-622, and its knockdown mimicked propofol's inhibitory effects.
- miR-622 targeted HOXA9, and propofol treatment decreased HOXA9 expression, with miR-622 overexpression suppressing glioma progression by reducing HOXA9.
Conclusions:
- Propofol exerts its tumor-suppressive effects in glioma by regulating the circMAPK4/miR-622/HOXA9 axis.
- This axis plays a critical role in controlling glioma cell growth, migration, invasion, and apoptosis in vitro.
- The findings elucidate a novel molecular mechanism for propofol's anti-glioma activity.
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