Propofol-Induced miR-493-3p Inhibits Growth and Invasion of Gastric Cancer through Suppression of DKK1-Mediated Wnt/β-Catenin Signaling Activation

Abstract

Purpose. Gastric cancer (GC) is one of the most common malignant tumors and also one of the most deadly tumors. In recent years, studies have shown that propofol can inhibit the proliferation and metastasis of many tumor cells. In the present study, we aimed to investigate the underlying mechanism of propofol inhibition of the growth and invasion of GC cells. Methods. Human gastric cancer cell line SGC-7901 and human normal gastric epithelial cell GES-1 were cultured in high-glucose Dulbecco’s Modified Eagle’s Medium (DMEM) supplemented with 10% fetal bovine serum at 37°C with 5% CO2. Propofol of different concentrations (0, 2, 5, and 10 μg/mL) was used to treat SGC-7901, and miR-493-3p inhibitor was transfected into SGC-7901. The cell proliferation of SGC-7901 was analyzed by MTT as well as colony formation assay. The qRT-PCR was used to assess the expression of mRNA for key genes. We examined the protein expression of DKK1 and relative markers with western blot. Putative binding places of miR-493-3p on the 3 ′ -untranslated area of DKK1 were predicted using bioinformatics and dual-luciferase method. Results. Propofol prohibited phenotypic features of GC, according to our findings. Furthermore, research into the underlying mechanisms of propofol’s suppressive effects in GC cell proved that propofol therapy improved the degrees of expression of the potential tumor suppressor miR-493-3p. The inhibiting properties of propofol on GC cell development, migration, and invasion were abolished when propofol-induced miR493-3p was silenced with anti-miR-493-3p. We also found that this drug reversed epithelial-mesenchymal transformation in SGC-7901 cells via inducing miR-493-3p. Propofol-induced miR-493-3p decreases GC cell development via targeting DKK1 and hence inhibits Wnt/β-catenin signaling, according to these findings. Conclusion. Propofol-induced miR-493-3p decreased GC cell development via targeting DKK1 and hence inhibited Wnt/β-catenin signaling, according to these findings.

REST Promotes Autophagy in Gastric Cancer by Transcriptionally Activating FABP6 to Inhibit the Akt/mTOR Signaling Pathway

“…Similarly, DKK1 has been shown to correlate with poorer sur- vival rates in GC patients, through mechanisms that involve the creation of an immunosuppressive tumor microenvironment [29]. Literature also suggests that DKK1 is targeted by anesthesia-induced miR-493-3p, which inhibits GC cell growth by repressing Wnt/β-catenin signaling and is implicated in GC cell invasion, proliferation, and drug resis-tance [30]. Given these precedents, FABP6 was selected as the focal prognostic marker for our study.…”

Tumor-derived CircRNA_102191 promotes gastric cancer and facilitates M2 macrophage polarization

“…Studies have found that miR-493-3p plays a tumor suppressor role in ovarian cancer, non-small cell lung cancer, laryngeal squamous cell carcinoma, and glioma [ 24–27 ]. Kaishuai Zhan et al found that miR-493-3p can be induced by propofol and inhibit the growth and invasion of gastric cancer by inhibiting the activation of Wnt/β-Catenin signal mediated by DKK1 [ 28 ]. We found that circRNA_102191 sponge adsorbed miR-493-3p through qRT-PCR and dual luciferase experiments, and miR-493-3p could reverse the effect of circRNA_102191 on the biological behavior of gastric cancer cells.…”

Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets

“…Various medications, including morphine, propofol, and sufentanil, have been used in clinical practice as part of PPC to prevent I/R injury. Previous studies have shown that morphine can activate Wnt/β-catenin signaling 491 – 493 ; propofol has a therapeutic effect against esophageal cancer, 494 gastric cancer, 495 hepatocellular carcinoma, 496 and colon cancer 497 by blocking Wnt/β-catenin signaling; Sufentanil inhibits the proliferation of lung cancer cells by suppressing Wnt/β-catenin signaling. 498 During PPC, Wnt/β-catenin signaling may be one of the molecular pathways involved in protecting organs from further damage.…”