A Circular RNA, hsa_circ_0018180 (circPARD3), Triggers Glycolysis and Promotes Malignancy of Head and Neck Squamous Cell Carcinoma Through the miR-5194/ENO1 Axis
A Circular RNA, hsa_circ_0018180 (circPARD3), Triggers Glycolysis and Promotes Malignancy of Head and Neck Squamous Cell Carcinoma Through the miR-5194/ENO1 Axis
复制标题
DOI：
10.1007/s10528-022-10253-0
复制
发表时间：
2022-07-28
影响因子：
2.4
通讯作者：
Zhang, Ze
中科院分区：
文献类型：
--
作者：
Luo, Jing-Tao;Wang, Ya-fei;Zhang, Ze
新的证据表明，环状 RNA (circRNA) 在调节多种人类癌症的恶性肿瘤和病理进展中发挥着关键作用。葡萄糖代谢重编程是一个被广泛认为有助于促进肿瘤发生的特征。尽管如此，它们对头颈鳞状细胞癌（HNSCC）细胞糖酵解的贡献仍有待进一步阐明。在此，我们的目的是研究 circRNA hsa_circ_0018180（也称为 circPARD3）在 HNSCC 中的作用。通过qRT-PCR测定circPARD3在HNSCC组织和不同细胞系中的表达模式及其与生存预后的相关性。进行 CCK-8、EdU 掺入和 Transwell 测定分别评估细胞活力、增殖、迁移和侵袭。通过进行糖酵解来评估葡萄糖摄取和乳酸产生。从机制上讲，circPARD3/miR-5194/ENO1 轴通过 RNA 免疫沉淀 (RIP) 和荧光素酶报告基因检测进行了验证。采用蛋白质印迹分析来测量上皮间质转化（EMT）相关的生物标志物。在 HNSCC 组织和细胞系中观察到的 circPARD3 上调表明患者预后不良。 circPARD3的稳定敲低对细胞活力、增殖、迁移和侵袭以及葡萄糖摄取和乳酸产生具有显着的抑制作用。从机制上讲，circPARD3 含有 miR-5194，充当 miRNA 海绵，从而增加 ENO1 表达。此外，ENO1 明显逆转了 miR-5194 介导的减弱的恶性行为。总的来说，我们的研究通过 circPARD3/miR-5194/ENO1 的新机制确定了 circPARD3 在 HNSCC 中的致癌作用，并为 HNSCC 提供了一个有前景的治疗靶点。
Emerging evidence has demonstrated the pivotal roles of circular RNAs (circRNAs) in the modulation of malignancy and pathological progression among multiple human cancers. Glucose metabolism reprogramming is a widely identified characteristic for contributing to facilitate tumorigenesis. Nonetheless, their contributions to head and neck squamous cell carcinoma (HNSCC) cell glycolysis remain to be further elucidated. Herein, we aim to investigate the role of circRNA, hsa_circ_0018180 (also named as circPARD3) in HNSCC. Expression patterns of circPARD3 in HNSCC tissues and different cell lines were determined by qRT-PCR assay, as well as its correlation with the prognosis of survival. CCK-8, EdU incorporation, and transwell assays were carried out to assess the cell viability, proliferation, migration, and invasion, respectively. Glucose uptake and lactate production were evaluated by preforming glycolysis. Mechanistically, the circPARD3/miR-5194/ENO1 axis was verified by RNA immunoprecipitation (RIP) and luciferase reporter assays. Western blot analysis was employed to measure the epithelial-mesenchymal transition (EMT)-associated biomarkers. Upregulated circPARD3 observed in HNSCC tissues and cell lines indicated the poor prognosis of patients. Stable knockdown of circPARD3 dramatically exerted the suppressive effects on cell viability, proliferation, migration, and invasion, as well as glucose uptake and lactate production. Mechanistically, circPARD3 harbored miR-5194, serving as a miRNA sponge, thereby increasing ENO1 expression. Moreover, ENO1 evidently reversed miR-5194-mediated attenuated malignant behaviors. Collectively, our study identified an oncogenic role of circPARD3 in HNSCC through a novel machinery of circPARD3/miR-5194/ENO1 and provided a promising therapeutic target for HNSCC.