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 circ86591, one of the isoforms of circular ANRIL, affects the progression of colorectal cancer (CRC). Real-time quantitative polymerase chain reaction (qRT-PCR) was utilized to examine circ86591 expression in cells. RNA pull-down, mass spectrometry, RNA immunoprecipitation, and western blotting (WB) were applied to elucidate molecular mechanisms underlying circ86591 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 circ86591. Circ86591 is lowly expressed in CRC cells overexpressing oncogenic linANRIL. Mechanistically, circ86591 directly interacts with ErbB3-binding protein (EBP1) and acetyl coenzyme A carboxylase (ACC1) proteins to modulate cell cycle and lipid metabolism. The knockdown of circ86591 by antisense oligonucleotide (ASO) increases the drug resistance of CRC cells to 5-FU, gemcitabine, or doxorubicin. Overexpression of circ86591 suppresses CRC growth both in vitro and in vivo 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.