CircPRRC2C通过MiR-136-5p/HOXD11轴促进喉鳞状细胞癌细胞的致癌表型。
CircPRRC2C Promotes the Oncogenic Phenotypes of Laryngeal Squamous Cell Carcinoma Cells via MiR-136-5p/HOXD11 Axis.
发表日期:2023 Sep 20
作者:
Xiu Peng, Xintian Chen, Shuai Peng, Yingming Chen, Yong Li, Yang Tian
来源:
Environmental Technology & Innovation
摘要:
循环RNA(circRNAs)在喉鳞状细胞癌(LSCC)的癌变中的参与逐渐被提出。因此,我们的目的是探索circPRRC2C在LSCC中的功能和机制。利用定量实时荧光聚合酶链反应(qRT-PCR)和蛋白质印迹法检测基因和蛋白质含量。通过使用5-乙炔基-2'-脱氧尿苷、集落形成、流式细胞术和转形单元实验进行体外实验。利用双荧光素酶报告基因试验确认miR-136-5p与circPRRC2C或Homeobox D11(HOXD11)的结合情况。建立小鼠异种移植模型进行体内分析。使用商业套件进行外泌体分离。CircPRRC2C是一种稳定的circRNA,在LSCC组织和细胞系中高表达。在功能上,circPRRC2C缺乏会损害体外LSCC细胞的增殖、迁移和侵袭,但会诱导细胞凋亡,并抑制体内肿瘤生长,然而,circPRRC2C的过表达则具有完全相反的效果。机制上,circPRRC2C直接靶向miR-136-5p,在LSCC细胞的生长和迁移中显示出抑制作用。同时,miR-136-5p直接靶向HOXD11,circPRRC2C/miR-136-5p/HOXD11构成了LSCC细胞中的反馈环路。进一步的拯救实验显示,circPRRC2C通过miR-136-5p/HOXD11轴发挥其效应。另外,circPRRC2C稳定地封装进外泌体,并显示出对LSCC的潜在诊断价值。CircPRRC2C作为一个促进LSCC细胞致癌表型的癌基因,通过miR-136-5p/HOXD11轴发挥其作用,此外,circPRRC2C稳定地封装进外泌体,表明circPRRC2C靶向药物在LSCC治疗中的潜在应用。©2023. 作者,授权给Springer Science+Business Media, LLC,归于Springer Nature。
The involvement of circular RNAs (circRNAs) in laryngeal squamous cell carcinoma (LSCC) carcinogenesis has gradually been proposed. Herein, we aimed to explore the function and mechanism of circPRRC2C in LSCC. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used for detecting the content of genes and proteins. In vitro experiments were conducted using 5-ethynyl-2'-deoxyuridine, colony formation, flow cytometry, and transwell assays. The binding between miR-136-5p and circPRRC2C or Homeobox D11 (HOXD11) was confirmed by using the dual-luciferase reporter assay. The murine xenograft model was established for in vivo analysis. The commercial kit was used for exosome separation. CircPRRC2C is a stable circRNA, and was highly expressed in LSCC tissues and cell lines. Functionally, circPRRC2C deficiency impaired LSCC cell proliferation, migration and invasion but induced cell apoptosis in vitro and impeded tumor growth in vivo, however, circPRRC2C overexpression showed the exact opposite effects. Mechanistically, circPRRC2C directly targeted miR-136-5p, which showed inhibitory effects on the growth and mobility of LSCC cells. Meanwhile, miR-136-5p directly targeted HOXD11, and circPRRC2C/miR-136-5p/HOXD11 formed a feedback loop in LSCC cells. Further rescue assays exhibited that circPRRC2C exerted its effects by miR-136-5p/HOXD11 axis. In addition, circPRRC2C was stably packaged into exosomes and showed potential diagnostic value for LSCC. CircPRRC2C acted as an oncogene to promote LSCC cell oncogenic phenotypes via miR-136-5p/HOXD11 axis, besides, circPRRC2C was stably packaged into exosomes, indicating the potential application of circPRRC2C-targeting agents in the treatment in LSCC.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.