Circ_0087851 suppresses colorectal cancer malignant progression through triggering miR-593-3p/BAP1-mediated ferroptosis

Abstract

BackgroundEmerging research has validated that circular RNAs (circRNAs) have indispensable regulatory functions in tumorigenesis, including colorectal cancer (CRC). Ferroptosis is a specific cell death form and implicates in the malignant progression of tumors. Here, this study aimed to investigate the biofunction of circ_0087851 in tumor progression and ferroptosis of CRC, as well as its underlying molecular mechanism.MethodsThe expression pattern of circ_0087851 in CRC was validated by qRT-PCR. The biological characteristics of circ_0087851 in CRC were assessed through CCK-8, colony formation and transwell assays in vitro. The ferroptosis was measured using ferroptosis-related reagents on iron, Fe2+, and lipid ROS detection. Bioinformatics, luciferase reporter, and RNA pulldown assays were employed to reveal the circ_0087851-mediated regulatory network. In addition, the effect of circ_0087851 on tumor growth in vivo was detected using a xenograft model.ResultsCirc_0087851 was notably diminished in CRC tissues and cells. Functionally, overexpression of circ_0087851 suppressed CRC cell growth, migration, invasion, and facilitated ferroptosis in vitro. Meanwhile, circ_0087851 upregulation impeded CRC growth in vivo. Mechanistically, circ_0087851 functioned as a molecular sponge for miR-593-3p, and BRCA1 associated protein 1 (BAP1) was identified as a downstream target of miR-593-3p. Besides, rescue experiments revealed that miR-593-3p overexpression or silencing of BAP1 reversed circ_0087851-mediated CRC progression.ConclusionCirc_0087851 performed as a tumor suppressor and ferroptosis promoter by the miR-593-3p/BAP1 axis, providing novel biomarker and therapeutic target for the clinical management of CRC.