Downregulation of SNORD20 promotes ferroptosis in corpus cavernosum smooth muscle cells from diabetic rats through inducing the mitochondrial dysfunction

Abstract

Erectile dysfunction (ED) disturbs the life of elderly men, and ferroptosis may be associated with the progression of ED. Small nucleolar RNAs (snoRNAs, 60-300 nucleotides) are non-coding regulatory RNAs mainly located in cell nucleolus, and SNORD20 was found to participate in the function of smooth muscle cells. However, the function of SNORD20 in ED remains unexplored. In the current research, protein and mRNA levels were examined using Western blot and RT-qPCR, respectively. Flow cytometry was employed to investigate apoptosis in cells. Mitochondrial function was examined using JC-1 and MitoSOX staining. Moreover, Fe²⁺ levels were examined using iron kits and an erectile function study in rats was conducted to further explore the function of SNORD20 in diabetic ED. It was revealed that SNORD20 level was reduced in cells obtained from diabetic ED rats. Notably, SNORD20 overexpression increased the proliferation in corpus cavernosum smooth muscle cells from diabetic rats, and SNORD20 small interfering RNA exerted the opposite effect. SNORD20 knockdown markedly promoted cell apoptosis and ferroptosis, and induced mitochondrial dysfunction. In addition, silencing of SNORD20 induces mitochondrial dysfunction and induced ferroptosis via downregulating Nrf2 and GPX4 expressions in corpus cavernosum smooth muscle cells. Moreover, SNORD20 overexpression alleviated the erectile function of diabetic rats in vivo. Collectively, SNORD20 knockdown may promote ferroptosis in corpus cavernosum smooth muscle cells obtained from diabetic ED rats through inducing mitochondrial dysfunction, highlighting that this snoRNA may acts as a key player in ED.

Keywords: Erectile dysfunction; Ferroptosis; Mitochondrial dysfunction; SNORD20.