Wu Mingyuan, Sun Tanlezi, Xing Lianjun
Department of Gastroenterology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Basic Medical College, Shanghai Medical College of Fudan University, Shanghai, China.
Cancer Biother Radiopharm. 2023 Dec;38(10):708-719. doi: 10.1089/cbr.2020.3779. Epub 2020 Oct 6.
Circular RNA (circRNA) can regulate the progression of hepatocellular carcinoma (HCC). However, the role and potential mechanism of circ_0004913 in HCC are not explored. Circ_0004913 was identified from two GSE datasets (GSE94508 and GSE97322) as a differentially expressed circRNA between HCC and normal tissues. Levels of circ_0004913, microRNA-184 (miR-184), and hepcidin () were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, migration, and invasion were estimated by methyl thiazolyl tetrazolium, colony formation, and Transwell assays, respectively. Levels of all proteins were examined by Western blot. Glucose consumption and lactate and ATP production were analyzed by the glucose, lactate, and ATP assay kits. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were performed to verify the interactions among miR-184 and circ_0004913 or . The mice xenograft models were established to assess the effect of circ_0004913 on tumor growth . Circ_0004913 was downregulated in HCC, and its expression impeded cell proliferation, migration, and invasion, EMT, and glycolysis in HCC cells. miR-184 was identified as a target miRNA of circ_0004913, and their expression levels were negatively correlated. miR-184 overexpression could reverse the inhibitory effect of circ_0004913 on HCC cell progression. Moreover, as a target gene of miR-184, expression was positively correlated with circ_0004913 expression in HCC tissues, and repression of miR-184 could inhibit the progression of HCC cells by increasing expression. Circ_0004913 could inhibit JAK2/STAT3/AKT signaling pathway and tumor growth by regulating the miR-184/ axis. Circ_0004913 inhibited the tumorigenesis of HCC by sponging miR-184 to regulate expression and .
环状RNA(circRNA)可调控肝细胞癌(HCC)的进展。然而,circ_0004913在HCC中的作用及潜在机制尚未得到探索。从两个GSE数据集(GSE94508和GSE97322)中鉴定出circ_0004913为HCC与正常组织之间差异表达的circRNA。通过定量实时聚合酶链反应(qRT-PCR)测定circ_0004913、微小RNA-184(miR-184)和铁调素()的水平。分别通过甲基噻唑基四氮唑、集落形成和Transwell实验评估细胞增殖、迁移和侵袭。通过蛋白质印迹法检测所有蛋白质的水平。使用葡萄糖、乳酸和ATP检测试剂盒分析葡萄糖消耗、乳酸和ATP生成情况。进行双荧光素酶报告基因、RNA免疫沉淀(RIP)和RNA下拉实验以验证miR-184与circ_0004913或之间的相互作用。建立小鼠异种移植模型以评估circ_0004913对肿瘤生长的影响。circ_0004913在HCC中表达下调,其表达抑制HCC细胞的增殖、迁移、侵袭、上皮-间质转化(EMT)和糖酵解。miR-184被鉴定为circ_0004913的靶标微小RNA,它们的表达水平呈负相关。miR-184过表达可逆转circ_0004913对HCC细胞进展的抑制作用。此外,作为miR-184的靶基因,在HCC组织中的表达与circ_0004913表达呈正相关,抑制miR-184可通过增加的表达来抑制HCC细胞的进展。circ_0004913可通过调节miR-184/轴抑制JAK2/STAT3/AKT信号通路和肿瘤生长。circ_0004913通过吸附miR-184调节表达和来抑制HCC的肿瘤发生。