Effect of cold atmospheric plasma (CAP) on the energy metabolism in HeLa cells through miRNA regulation

Cold atmospheric plasma (CAP) is an emerging tool for tumor treatment because it can inhibit cancer cell proliferation primarily through oxidative stress due to CAP-induced reactive oxygen species (ROS). Among various ROS targeting molecules in cancer cells, microRNAs (miRNAs) are one kind of important targets that can be stimulated by ROS, and many studies have shown that miRNAs are involved in the metabolism regulation of cancer cells. In this study, we applied helium-CAP (He-CAP) to HeLa cells, and observed that the ROS induced by He-CAP could modulate the miRNAs related to energy metabolism, leading to the changes of proliferation, glycolysis, tricarboxylic acid (TCA) cycling and oxidative phosphorylation (OXPHOS) in the HeLa cells, and affected the related hypoxia-inducible factor 1, p53, phosphoinositide 3-kinase signaling pathways. In addition, the analysis of miRNAs in the metabolic network revealed that the expressions of the miRNAs responsible for the promotion of energy metabolism increased, and correspondingly, the involved mRNA and protein expression decreased. As such, this study has not only demonstrated that CAP treatment could significantly change the miRNAs expression of cancer cells, but also provided a more in-depth understanding of the CAP effects on glycolysis, TCA cycling and OXPHOS processes in the cells through the comprehensive analysis of the miRNAs regulation.