Department of Clinical Oncology, The Affiliated Hospital of Shandong University of TCM, Jinan, Shandong, China.
Department of Respiratory Diseases, The First Clinical Medical College of Shandong University of TCM, Jinan, Shandong, China.
Biomed Pharmacother. 2021 Jun;138:111439. doi: 10.1016/j.biopha.2021.111439. Epub 2021 Mar 6.
Curcumin exerts a suppressive effect in tumor growth by acting as a modulator of multiple molecular targets. Circular RNA hsa_circ_0007580 (circ-PRKCA) accelerates the tumorigenesis of non-small cell lung cancer (NSCLC). However, whether curcumin can regulate circ-PRKCA to inhibit NSCLC progression is unclear.
Cell viability, colony formation, apoptosis, migration, and invasion were analyzed using Cell Counting Kit-8 (CCK-8), plate clone, flow cytometry, or transwell assay. Expression of circ-PRKCA, microRNA (miR)-384, and ITGB1 mRNA (integrin subunit beta 1) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Curcumin repressed NSCLC growth through regulating circ-PRKCA expression was validated by xenograft assay. The targeting relationship between circ-PRKCA or ITGB1 and miR-384 was verified by dual-luciferase reporter assay. The level of ITGB1 protein was measured by western blotting.
Circ-PRKCA and ITGB1 expression were elevated in NSCLC tissues and cells, but miR-384 had an opposing tendency. After curcumin treatment, the expression tendency of circ-PRKCA, miR-384, and ITGB1 in NSCLC cells was overturned. Furthermore, curcumin impeded viability, colony formation, migration, invasion, and accelerated apoptosis of NSCLC cells, but these impacts were partially reversed by circ-PRKCA elevation, miR-384 downregulation, or ITGB1 overexpression. Also, the inhibitory effect of curcumin on xenograft tumor was further enhanced after circ-PRKCA knockdown. Notably, circ-PRKCA regulated ITGB1 expression through sponging miR-384 in curcumin-treated NSCLC cells.
Curcumin inhibited NSCLC growth through downregulating circ-PRKCA, which regulated ITGB1 expression by adsorbing miR-384. This study provided a new mechanism to understand how curcumin inhibited the progression of NSCLC.
姜黄素通过作为多个分子靶点的调节剂发挥抑制肿瘤生长的作用。环状 RNA hsa_circ_0007580（circ-PRKCA）加速了非小细胞肺癌（NSCLC）的肿瘤发生。然而，姜黄素是否可以调节 circ-PRKCA 来抑制 NSCLC 进展尚不清楚。
使用细胞计数试剂盒-8（CCK-8）、平板克隆、流式细胞术或 Transwell 测定法分析细胞活力、集落形成、细胞凋亡、迁移和侵袭。通过定量实时聚合酶链反应（qRT-PCR）检测 circ-PRKCA、microRNA（miR）-384 和 ITGB1 mRNA（整合素亚基β 1）mRNA 的表达。通过异种移植实验验证姜黄素通过调节 circ-PRKCA 表达抑制 NSCLC 生长。通过双荧光素酶报告基因实验验证 circ-PRKCA 或 ITGB1 与 miR-384 的靶向关系。通过 Western blot 测定 ITGB1 蛋白水平。
circ-PRKCA 和 ITGB1 在 NSCLC 组织和细胞中表达上调，而 miR-384 则呈相反趋势。姜黄素处理后，NSCLC 细胞中 circ-PRKCA、miR-384 和 ITGB1 的表达趋势发生逆转。此外，姜黄素抑制 NSCLC 细胞活力、集落形成、迁移、侵袭并加速细胞凋亡，但这些影响部分被 circ-PRKCA 上调、miR-384 下调或 ITGB1 过表达逆转。此外，在敲低 circ-PRKCA 后，姜黄素对异种移植肿瘤的抑制作用进一步增强。值得注意的是，姜黄素处理的 NSCLC 细胞中，circ-PRKCA 通过吸附 miR-384 调节 ITGB1 表达。本研究为了解姜黄素抑制 NSCLC 进展的机制提供了新的思路。
