CircABCB10 silencing inhibits the cell ferroptosis and apoptosis by regulating the miR-326/CCL5 axis in rectal cancer

Zhen-Yu Xian, Bang Hu, Ting Wang, Jin-Lin Cai, Jun-Yi Zeng, Qi Zou,  Pei-Xuan Zhu

Abstract:

Circular ATP binding cassette subfamily B member 10 (circABCB10) has been identified to have oncological functions in several tumors. However, the roles of circABCB10 in rectal cancer remain unknown. The expression of circABCB10, microRNA (miR)-326 and C-C motif chemokine ligand 5 (CCL5), and apoptosis related-protein was detected using quantitative real-time polymerase chain reaction or western blot, respectively. Cell survival or apoptosis was measured using cell counting kit-8 assay or flow cytometry. The accumulations of intracellular lipid reactive oxygen species (ROS) and Fe2+ were analyzed using C11-BODIPY dye or iron kit assay, respectively. In vivo experiments were conducted using the murine xenograft model. The interaction between miR-326 and circABCB10 or CCL5 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. CircABCB10 and CCL5 were upregulated but miR-326 was downregulated in rectal cancer. The knockdown of circABCB10 promoted rectal cancer cell ferroptosis and apoptosis in vitro as well as inhibited tumor growth in vivo. miR-326 was a target of circABCB10, and the miR-326 inhibition could partially attenuate circABCB10 deletion-induced cell ferroptosis and apoptosis. miR-326 directly interacted with CCL5, and the miR-326 inhibition suppressed cell ferroptosis and apoptosis by targeting CCL5. Besides, we observed that miR-326 was negatively regulated by circABCB10, while CCL5 was positively regulated by it, and circABCB10 served as a sponge of miR-326 to regulate the CCL5 expression in rectal cancer cells. CircABCB10 silence promoted rectal cancer cell ferroptosis and apoptosis by regulating the miR-326/CCL5 axis, suggesting a potential therapeutic target for rectal cancer therapy.