Abstract
BackgroundPropofol is commonly used for anesthesia during surgery and has been demonstrated to inhibit cancer development, which is shown to be associated with deregulation of non-coding RNAs (ncRNAs). The objective of this study was to explore the role of circular RNA mucin 16 (circ_MUC16) in Propofol-mediated inhibition of ovarian cancer.MethodsThe expression of circ_MUC16, microRNA-1182 (miR-1182) and S100 calcium-binding protein B (S100B) mRNA was measured by quantitative real-time polymerase chain reaction (qPCR). The expression of S100B protein was checked by western blot. Cell proliferation was assessed by 3-(4, 5-di methyl thiazol-2-yl)-2, 5-di phenyl tetrazolium bromide (MTT) assay and colony formation assay. Glycolysis metabolism was assessed by glucose consumption, lactate production and ATP level. Cell migration and cell invasion were assessed by transwell assay. Cell migration was also assessed by wound healing assay. Animal study was conducted in nude mice to determine the role of circ_MUC16 in vivo. The relationship between miR-1182 and circ_MUC16 or S100B was validated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay.ResultsPropofol inhibited ovarian cancer cell proliferation, glycolysis metabolism, migration and invasion, which were partly recovered by circ_MUC16 overexpression. Circ_MUC16 was downregulated in Propofol-treated ovarian cancer cells. Besides, circ_MUC16 knockdown enhanced the effects of Propofol to further inhibit tumor growth in vivo. MiR-1182 was a target of circ_MUC16, and circ_MUC16 knockdown-inhibited cell proliferation, glycolysis metabolism, migration and invasion were partly restored by miR-1182 inhibition. In addition, S100B was a target of miR-1182, and miR-1182-suppressed cell proliferation, glycolysis metabolism, migration and invasion were partly restored by S100B overexpression.ConclusionCirc_MUC16 overexpression alleviated the effects of Propofol to promote the aggressive behaviors of ovarian cancer by targeting the miR-1182/S100B network.
Highlights
Propofol is commonly used for anesthesia during surgery and has been demonstrated to inhibit cancer development, which is shown to be associated with deregulation of non-coding RNAs
We found that Propofol hardly affected the viability of IOSE-80 cells (Fig. 1A), while Propofol significantly depleted the viability of A2780 and SK-OV-3 cells in a dose-dependent manner (Fig. 1B and C), suggesting that Propofol had vital effects on ovarian cancer cells
Propofol markedly weakened the capacities of migration and invasion in A2780 and (See figure on page.) Fig. 1 Propofol inhibited A2780 and SK-OV-3 cell proliferation, glycolysis, migration and invasion
Summary
Propofol is commonly used for anesthesia during surgery and has been demonstrated to inhibit cancer development, which is shown to be associated with deregulation of non-coding RNAs (ncRNAs). The objective of this study was to explore the role of circular RNA mucin 16 (circ_MUC16) in Propofol-mediated inhibition of ovarian cancer. In 2018, there were estimated 295,414 new cases and 184,799 deaths worldwide of ovarian cancer [1]. Morphological and molecular studies of ovarian cancer indicate that it should not be classified as a single disease, but should be attributed to a collection of disease subtypes with distinct origins and clinical behaviors [14, 11]. It is necessary to explore the pathogenesis of ovarian cancer from multiple levels to improve treatment strategies
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