circ86591's suppression of colorectal cancer cell proliferation via cell cycle and metabolic regulation

Circular ribonucleicacids (circRNAs), marked by their covalently closed-loop structures, serve as crucial regulators in tumor development and progression. This study aimed to explore how <italic>circ86591</italic>, one of the isoforms of circular <italic>ANRIL</italic>, affects the progression of colorectal cancer (CRC). Real-time quantitative polymerase chain reaction (qRT-PCR) was utilized to examine <italic>circ86591</italic> expression in cells. RNA pull-down, mass spectrometry, RNA immunoprecipitation, and western blotting (WB) were applied to elucidate molecular mechanisms underlying <italic>circ86591</italic> and its binding proteins. RNA-sequencing, along with gain- and loss-of function assays, was conducted to uncover the tumor-suppressive effect and the relevant signaling pathways of <italic>circ86591</italic>. <italic>Circ86591</italic> is lowly expressed in CRC cells overexpressing oncogenic <italic>linANRIL</italic>. Mechanistically, <italic>circ86591</italic> directly interacts with ErbB3-binding protein (EBP1) and acetyl coenzyme A carboxylase (ACC1) proteins to modulate cell cycle and lipid metabolism. The knockdown of <italic>circ86591</italic> by antisense oligonucleotide (ASO) increases the drug resistance of CRC cells to 5-FU, gemcitabine, or doxorubicin. Overexpression of <italic>circ86591</italic> suppresses CRC growth both <italic>in vitro</italic> and <italic>in vivo</italic> via upregulation of P53 and negative feedback of the protein kinase B (AKT) pathway. Combining circ86591 adenovirus (ADV) with the anti-lipid metabolism drug CMS121 yields synergistic anti-tumor effects. In conclusion, the circ86591 inhibits CRC progression and holds potential as a therapeutic target for those tumors with active lipid metabolism.