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.
Metastasis is the leading cause of death in patients with lung adenocarcinoma (LUAD), highlighting the urgent need to identify novel therapeutic targets. GLIS family zinc finger 1 (GLIS1) is a transcription factor implicated in multiple cancers. However, its role in LUAD remains poorly defined. In this study, we first identified that GLIS1 was significantly upregulated in LUAD tissues. To modulate its expression, lentiviral vectors were constructed to knock down or overexpress GLIS1 in NCI-H1975 and A549 LUAD cell lines, respectively. In vitro gain- and loss-of-function experiments revealed that GLIS1 knockdown significantly inhibited the migratory and invasive capabilities of NCI-H1975 cells. Conversely, GLIS1 overexpression enhanced these malignant phenotypes in A549 cells. In vivo study demonstrated that GLIS1 knockdown substantially reduced liver and lung metastasis of NCI-H1975 cells in mice. Furthermore, we found that downregulation of GLIS1 suppressed LUAD cell migration by inhibiting Homeobox A9 (HOXA9) methylation, which led to the subsequent upregulation of HOXA9 expression. Mechanistically, GLIS1 knockdown transcriptionally suppressed the mRNA level of the DNA methyltransferase DNMT3B, thereby attenuating HOXA9 methylation. Specifically, overexpression of DNMT3B led to DNA hypermethylation and transcriptional suppression of HOXA9, thereby partially rescuing the tumor-suppressive effects resulting from GLIS1 knockdown. Our work is the first to implicate the GLIS1/DNMT3B axis in the epigenetic silencing of HOXA9 in LUAD, highlighting the therapeutic potential of targeting GLIS1.
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