Lauric acid epigenetically regulates lncRNA HOTAIR by remodeling chromatin H3K4 tri-methylation and modulates glucose transport in SH-SY5Y human neuroblastoma cells: Lipid switch in macrophage activation

Lauric acid (LA) induces apoptosis in cancer and promotes the proliferation of normal cells by maintaining cellular redox homeostasis. Earlier, we postulated LA-mediated regulation of the NF-kappa B pathway by an epigenetic mechanism. However, the molecular mechanism and possible epigenetic events remained enigmatic. Herein, taking the lead from the alteration in cellular energetics in cancer cells upon LA exposure, we investigated whether LA exposure can epigenetically influence lncRNA HOTAIR, regulate glucose metabolism, and shift the cellular energetic state. Our results demonstrate LA induced modulation of lncRNA HOTAIR in a dose and time dependent manner. In addition, HOTAIR induces the expression of glucose transporter isoform 1 (GLUT1) and is regulated via NF-kappa B activation. Silencing HOTAIR by siRNA-mediated knockdown suppressed GLUT1 expression suggesting the key role of HOTAIR in LA-mediated metabolic reprogramming. Further, from our ChIP experiments, we observed that silencing HOTAIR subdues the recruitment of NF-kappa B on the GLUT1 (SLC2A1) promoter region. In addition, by performing western blot and immunocytochemistry studies, we found a dose dependent increase in Histone 3 Lysine 4 tri-methylation (H3K4me3) in the chromatin landscape. Taken together, our study demonstrates the epigenetic regulation in LA-treated SH-SY5Y cancer cells orchestrated by remodeling chromatin H3K4me3 and modulation of lncRNA HOTAIR that apparently governs the GLUT1 expression and regulates glucose uptake by exerting transcriptional control on NF-kappa B activation. Our work provides insights into the epigenetic regulation and metabolic reprogramming of LA through modulation of lncRNA HOTAIR, remodeling chromatin H3K4 tri-methylation, and shifting the energy metabolism in SH-SY5Y neuroblastoma cells.

Automated summary

This study reveals that Lauric acid (LA) exerts an epigenetic regulation and metabolic reprogramming on SH-SY5Y neuroblastoma cells through modulation of lncRNA HOTAIR, remodeling of chromatin H3K4 tri-methylation and regulation of glucose uptake by controlling NF-kappa B activation.