Luo Ruiying, Li Shuang, Yang Chi, Tang Baoyuan, Li Long, Luo Changjiang
Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730000, Gansu, China.
Department of respiratory medicine, The Third People's Hospital of Gansu Province, Lanzhou, 730000, Gansu, China.
Cell Biochem Biophys. 2025 Mar;83(1):377-390. doi: 10.1007/s12013-024-01466-8. Epub 2024 Aug 5.
Pancreatic cancer (PC) is a common gastrointestinal cancer with high invasiveness and high mortality. Curcumin is a natural polyphenol with anti-tumor activity against different cancers, including PC. Curcumin has been verified to mediate the expression of circular RNAs (circRNAs) to inhibit tumor development. This study aimed to explore the function and regulatory mechanism of curcumin on circ_0079440 in PC. PC cells were treated with different concentrations of curcumin (0, 5, 10 or 15 μM) for 24 h. Gene expression in PC cells and tissues was detected using RT-qPCR. Cell malignant phenotypes were determined by functional assays. The levels of EMT-related proteins were tested using western blot. RNA interaction was determined using RNA pulldown assay, luciferase reporter assay and RIP assay. The results showed that curcumin suppressed cell proliferative, migratory, and invasive capabilities, and weakened epithelial-mesenchymal transition (EMT) in a concentration-dependent way. Circ_0079440 was expressed at a high level in PC and its level was reduced via curcumin administration in PC cells. Rescue assays showed that circ_0079440 overexpression reversed the suppressive effects of curcumin on PC cell malignant phenotypes. Furthermore, in the xenograft mouse models, curcumin treatment inhibited tumor growth and metastasis, and circ_0079440 upregulation reversed the function of curcumin. Additionally, circ_0079440 was revealed to bind to miR-522-3p to upregulate eukaryotic initiation factor 4A1 (EIF4A1) expression in PC cells. EIF4A1 expression was also downregulated by curcumin, and EIF4A1 overexpression abolished the suppressive functions of curcumin. Moreover, EIF4A overexpression or miR-522-3p inhibition counteracted the anti-tumor effects of circ_0079440 depletion on PC development. To sum up, curcumin suppresses PC development by targeting the circ_0079440/miR-522-3p/EIF4A1 pathway, which might provide novel therapeutic targets for treatment of PC.
胰腺癌(PC)是一种常见的胃肠道癌症,具有高侵袭性和高死亡率。姜黄素是一种天然多酚,对包括胰腺癌在内的不同癌症具有抗肿瘤活性。已证实姜黄素可介导环状RNA(circRNA)的表达以抑制肿瘤发展。本研究旨在探讨姜黄素对胰腺癌中circ_0079440的作用及其调控机制。用不同浓度(0、5、10或15μM)的姜黄素处理胰腺癌细胞24小时。采用RT-qPCR检测胰腺癌细胞和组织中的基因表达。通过功能实验确定细胞的恶性表型。用蛋白质免疫印迹法检测上皮-间质转化(EMT)相关蛋白的水平。采用RNA下拉实验、荧光素酶报告基因实验和RNA免疫沉淀实验确定RNA相互作用。结果表明,姜黄素以浓度依赖的方式抑制细胞增殖、迁移和侵袭能力,并减弱上皮-间质转化。circ_0079440在胰腺癌中高表达,在胰腺癌细胞中通过给予姜黄素可使其水平降低。挽救实验表明,circ_0079440过表达可逆转姜黄素对胰腺癌细胞恶性表型的抑制作用。此外,在异种移植小鼠模型中,姜黄素治疗可抑制肿瘤生长和转移,而circ_0079440上调可逆转姜黄素的作用。此外,研究发现circ_0079440与miR-522-3p结合,上调胰腺癌细胞中真核起始因子4A1(EIF4A1)的表达。姜黄素也下调EIF4A1的表达,EIF4A1过表达消除了姜黄素的抑制作用。此外,EIF4A过表达或miR-522-3p抑制可抵消circ_0079440缺失对胰腺癌发展的抗肿瘤作用。综上所述,姜黄素通过靶向circ_0079440/miR-522-3p/EIF4A1通路抑制胰腺癌发展,这可能为胰腺癌的治疗提供新的治疗靶点。
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