Zinc Oxide Nanoparticle Inhibits Tumorigenesis of Renal Cell Carcinoma by Modulating Lipid Metabolism Targeting miR-454-3p to Repressing Metabolism Enzyme ACSL4

Abstract

Background. Renal cell carcinoma (RCC) affects the life quality of patients with advanced diseases despite good prognosis and exhibits abnormal lipid metabolism. Zinc oxide nanoparticles (ZONs) are metal oxide nanoparticles that are regarded as promising therapeutic candidate for multiple diseases. This study was for exploring the function of ZONs in RCC. Methods. We established in vitro cell model and in vivo xenograft model to determine the antitumor effect of ZONs. Cell viability and proliferation were evaluated via the cell counting kit-8 (CCK-8), colony formation, and 5-ethynyl-2’-deoxyuridine (EDU) assay. Protein and RNA levels were checked by using immunohistochemistry (IHC) and qRT-PCR assay. ROS, malondialdehyde (MDA), triglyceride, and total cholesterol were quantified to assess lipid oxidation and synthesis. Oil red O staining was performed to check lipid droplets accumulation. The ACSL4 and miR-454-3p expression in tumor samples and normal tissues were evaluated. The luciferase reporter gene assay was performed for checking the interaction between miR-454-3p and ACSL4 3’UTR region. Results. ZONs suppressed the proliferation and viability of RCC cells both in vitro and in vivo. ZONs suppressed accumulation of ROS, MDA, triglyceride, total cholesterol, and lipid droplets in RCC cells, along with upregulated miR-454-3p. miR-454-3p targeted the 3’UTR region to suppress its expression. In patient samples, ACSL4 expression was notably elevated and indicated poor prognosis of RCC patients. Conclusion. ZONs treatment notably impeded proliferation, lipid accumulation, and oxidation in RCC cells, through upregulating miR-454-3p to suppression the function of ACSL4. Our data suggested that ZONs are promising and effective agent for RCC treatment.