Hsa_circ_0050900 affects ferroptosis in intrahepatic cholangiocarcinoma cells by targeting hsa‑miR-605‑3p to regulate SLC3A2

Intrahepatic cholangiocarcinoma (ICC) is a highly lethal hepatobiliary tumor with high aggressiveness. The role of circular RNA (circRNA) in ICC remains to be explored. The present study aimed to investigate whether hsa_circ_0050900 affected ferroptosis in ICC cells by regulating hsa-microRNA (miR)-605-3p/solute carrier family 3 member 2 (SLC3A2). Human ICC cells were cultured and hsa_circ_0050900 expression was evaluated by reverse transcription-quantitative PCR. hsa_circ_0050900 was knocked down and ferroptosis inhibitor ferrostatin-1 was added to HuCCT-1 cells. Following knockdown or overexpression of hsa-miR-605-3p, Fe(2+), reactive oxygen species (ROS), glutathione peroxidase 4 and SLC3A2 levels were assessed using iron and ROS assay kit or RT-qPCR and western blotting, respectively. Cell function experiments were performed to examine proliferation and migration abilities. Dual-luciferase reporter gene and argonaute2-RNA immunoprecipitation assay verified the relationship among hsa_circ_0050900, hsa-miR-605-3p, and SLC3A2. hsa_circ_0050900 was derived from actinin alpha 4 gene and was elevated in ICC cells. Among HuCCT-1, QBC-939, HCCC-9810, and RBE cell lines, the highest expression was in HuCCT-1 cells. Inhibition of hsa_circ_0050900 inhibited proliferation and migration by facilitating ICC cell ferroptosis. hsa-miR-605-3p expression was elevated after knocking down hsa_circ_0050900 and hsa-miR-605-3p was negatively regulated by hsa_circ_0050900. In addition, hsa-miR-605-3p targeted SLC3A2. Overexpression of hsa-miR-605-3p regulated SLC3A2 to promote ICC cell ferroptosis and inhibit proliferation and migration. Taken together, knockdown of hsa_circ_0050900 inhibited SLC3A2 expression via sponging hsa-miR-605-3p to promote ICC cell ferroptosis, and finally suppressed proliferation and migration. The present study suggested that hsa_circ_0050900 was a potential therapeutic target for ICC.