Circular RNA ZFR promotes cell cycle arrest and apoptosis of colorectal cancer cells via the miR-147a/CACUL1 axis.

Background: Colorectal cancer (CC) is one of the most prevalent malignancies worldwide. Nonetheless, its pathogenicity and molecular mechanisms have not been completely elucidated yet. The potential clinical value of circular RNAs (circRNAs) in tumor diagnosis, treatment, and prognosis has received considerable attention.

Methods: Here, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) examined the levels of circular ZFR (circZFR) in CC cells. The expression of circZFR was knocked down in CC cells and cell viability was detected using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell cycle progression was assessed by flow cytometry and the expression levels of cyclin-associated proteins were detected by western blot analysis. The transferase dUTP nick end labeling (TUNEL) assay was used to detect apoptosis and western blot analysis was used to evaluate the expression levels of apoptosis-associated proteins. Subsequently, the interactions between circZFR and microRNA (miR)-147a and between miR-147a and CDK2 associated cullin domain 1 (CACUL1) were predicted by the Encyclopedia of RNA Interactomes database and verified by luciferase reporter assays. Finally, plasmid transfection, CCK-8, and flow cytometry assays were used to explore the associated mechanism of action.

Results: CircZFR was highly expressed in CC cell lines. Interference with its expression inhibited proliferation and induced G1/S cell cycle arrest and apoptosis in CC cells. The expression levels of miR-147a and CACUL1 were decreased and increased, respectively, in CC cells. These data demonstrated that circZFR could target miR-147a and CACUL1 to regulate the cell cycle and apoptosis of CC cells and, ultimately, promote the progression of CC.

Conclusions: Knockdown of the expression of circZFR upregulated miR-147a expression and reduced CACUL1 expression levels, thereby inhibiting the proliferation of CC cells and inducing cell cycle arrest and apoptosis.