Hsa_circ_0050900 affects ferroptosis in intrahepatic cholangiocarcinoma cells by targeting hsa‑miR-605‑3p to regulate SLC3A2.
Hsa_circ_0050900 affects ferroptosis in intrahepatic cholangiocarcinoma cells by targeting hsa‑miR-605‑3p to regulate SLC3A2.
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DOI：
10.3892/ol.2023.14135
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发表时间：
2024-01
期刊：
影响因子：
2.9
通讯作者：
Qiao S
中科院分区：
文献类型：
--
作者：
Shi X;Yang J;Wang M;Xia L;Zhang L;Qiao S
肝内胆管癌（ICC）是一种高致死率、高侵袭性的肝胆肿瘤。环状RNA （circRNA）在ICC中的作用仍有待探索。本研究旨在探讨hsa_circ_0050900是否通过调节hsa-microRNA (miR)-605-3p/溶质载体家族3成员2 （SLC3A2）影响ICC细胞铁凋亡。培养人ICC细胞，通过逆转录-定量PCR检测hsa_circ_0050900的表达。敲除hsa_circ_0050900，并在HuCCT-1细胞中加入铁下垂抑制剂ferrostatin-1。在敲低或过表达hsa-miR-605-3p后，分别使用铁和ROS检测试剂盒或RT-qPCR和western blotting评估Fe2+、活性氧（ROS）、谷胱甘肽过氧化物酶4和SLC3A2水平。细胞功能实验检测细胞的增殖和迁移能力。双荧光素酶报告基因和argonaute2-RNA免疫沉淀实验验证了hsa_circ_0050900、hsa-miR-605-3p和SLC3A2之间的关系。hsa_circ_0050900来源于actitinin α 4基因，在ICC细胞中表达升高。在HuCCT-1、QBC-939、hcc -9810和RBE细胞系中，HuCCT-1细胞的表达量最高。抑制hsa_circ_0050900通过促进ICC细胞铁下垂来抑制增殖和迁移。hsa-miR-605-3p在敲低hsa_circ_0050900后表达升高，hsa-miR-605-3p被hsa_circ_0050900负向调节。此外，hsa-miR-605-3p靶向SLC3A2。过表达hsa-miR-605-3p调控SLC3A2，促进ICC细胞铁下垂，抑制增殖和迁移。综上所述，敲低hsa_circ_0050900可通过海绵处理hsa-miR-605-3p抑制SLC3A2的表达，促进ICC细胞铁下垂，最终抑制细胞增殖和迁移。本研究提示hsa_circ_0050900是ICC的潜在治疗靶点。
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, Fe2+, 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.
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