P3H4 affects renal carcinoma through up-regulating miR-1/133a.

Abstract

P3H4, as a kind of quinone compounds, is a coenzyme Q10 (ubiquinone) analogues. A recent study investigated the role of P3H4 on cerebral ischemia-reperfusion and hypertension. It is well known that ischemia-reperfusion is closely associated with kidney disease. This study aims to investigate the impact of P3H4 in the occurrence and development of the tumor. A total of 40 rats at 8-week old were selected to establish renal cancer model by burying suture method for 4 months. The rats in the experimental group received P3H4 treatment at 100 mg/kg every 48 h for consecutive 4 weeks, while the rats in control received normal saline. H&E staining was applied to test the histological changes of tissue at 0, 1, 2 weeks after treatment. Gene microarray was adopted to screen miRNA expression to explore the function of miRNA in renal cancer cell line. Renal cancer cell migration and invasion were evaluated by wound healing and transwell assays after the treatment of P3H4, miR-1a, miR-133a, respectively. The rats were randomly equally divided into experimental group and control. HE staining result showed renal interstitial fibroblasts hyperplasia, renal tubular necrosis, and glomerular reduction after modeling. P3H4 treatment significantly alleviated the lesion severity and inhibited the tumor cells invasion. Microarray demonstrated that miR-1a and miR-133a were significantly upregulated in rat renal cancer tissue after the treatment of P3H4. The overexpression of miR-1a and miR-133a markedly reduced renal cell invasion and migration, which was consistent with the effect of P3H4. P3H4 suppressed the development of renal carcinoma through upregulating miR-1a and miR-13a, which provides fundamental leads for the future anti-cancer therapy.