RETRACTED: CircSETD3 (Hsa_circ_0000567) Suppresses Hepatoblastoma Pathogenesis via Targeting the miR-423-3p/Bcl-2-Interacting Mediator of Cell Death Axis

Abstract

Background: Up until now, the role of circSETD3 (Has_circ_0000567) in regulating cancer development has been reported in several tumors, but the role and regulatory mechanism of circSETD3 in hepatoblastoma (HB) remain unclear.Methods: The qPCR and western blotting were used to determine the mRNA and protein levels in the present study. Stability of circular RNA was detected by RNA digested experiments. The gain-of-function and rescue experiments were used to explore the function and mechanism of circSETD3 in HB. Cell counting kit-8, colony formation, transwell assay, and xenograft mice model were used to detect effects and regulatory mechanism of circSETD3/miR-423-3p/Bim axis on cell aggressive phenotype in vitro and in vivo.Results: Here, we identified that circSETD3 downregulated in both HB clinical tissues and cell lines, compared to that of normal tissues and cells. Further gain-of-function experiments validated that circSETD3 overexpression inhibited cell proliferation, viability, migration, epithelial-mesenchymal transition (EMT) and tumorigenesis, and induced cell apoptosis in HB cells. Next, we validated that miR-423-3p targeted both circSETD3 and 3′ untranslated region (3′UTR) of Bim, and circSETD3 positively regulated Bim in HB cells through sponging miR-423-3p in a competing endogenous RNA (ceRNA)-dependent manner. Furthermore, through conducting reversal experiments, we evidenced that the inhibiting effects of circSETD3 overexpression on HB development were abrogated by upregulating miR-423-3p and downregulating Bim.Conclusion: Taken together, we evidenced that circSETD3 sponged miR-423-3p to upregulate Bim, resulting in the inhibition of HB development.

An Update on Circular RNA in Pediatric Cancers

“…Furthermore, low expression of circSETD3 has been shown in advanced stages of disease and to be associated with poor survival in HB patients. These results indicate that circSETD3 acts as a tumor suppressor in HB, and functional experiments on this tumor demonstrated that its expression inhibits cell proliferation, migration, epithelial-to-mesenchymal transition (EMT) and induces apoptosis via sponging miR-423-3p to promote Bim expression [71].…”

MiR206 and 423-3p Are Differently Modulated in Fast and Slow-Progressing Amyotrophic Lateral Sclerosis Patients

“…MiR423-3p was found upregulated in slow compared to fast-progressing ALS patients (related to MRC PI), once controlled for months from the disease onset, ALSFRS-R score, total MRC score. MiR423-3p was previously demonstrated to inhibit Bim, an important pro-apoptotic protein in cancers (X. Li et al, 2021 ), which has been demonstrated to be down-modulated in a slow-progressing ALS mouse model (Matus et al, 2013 ). Bim silencing also decreased Bax recruitment to mitochondria and cytochrome c redistribution in a SOD1 murine neuroblastoma cell line (Soo et al, 2012 ).…”

The function and regulation network mechanism of circRNA in liver diseases

“…Circ_0015756 was found significantly up-regulated in human hepatoblastoma tissues and cell lines and circ_0015756 siRNA decreased the viability, proliferation and invasion ability of hepatoblastoma cells in vitro by sponging miR-1250-3p [155]. Li et al [156] demonstrated that circSETD3 downregulated in Hepatoblastoma tissues and cell lines, and it exerted as a tumor suppressor to inhibit proliferation, migration, EMT process, and induce apoptosis by miR-423-3p/Bim axis.…”