Tang Wenjun, Xu Junnv, Lin Shu, Luo Jingru, Zhuang Xiaohong, Qian Xiaoying, Zhang Chengsheng
Internal Medicine-Oncology, The Second Affiliated Hospital of Hainan Medical University, Haikou City, 570311, Hainan Province, China.
Internal Medicine-Oncology, The Second Affiliated Hospital of Hainan Medical University, Haikou City, 570311, Hainan Province, China.
Exp Cell Res. 2025 Jul 15;450(2):114685. doi: 10.1016/j.yexcr.2025.114685. Epub 2025 Jul 23.
Previous researches have indicated the oncogenic effect of circCOL1A2 in several cancers, such as tongue squamous cell carcinoma, gastric cancer, and colorectal cancer. Regrettably, the functions and mechanisms of circCOL1A2 in lung cancer, a disease with the highest global incidence and mortality rates and with 85 % of cases classified as non-small cell lung cancer (NSCLC), remain largely unexplored. Hsa_circ_0081111 (circCOL1A2) was identified from GSE236879 dataset of Gene Expression Omnibus (GEO) database. Its expression was validated in 37 paired samples of cancerous and adjacent normal tissues from NSCLC patients, as well as in cell lines. The function of hsa_circ_0081111 was analyzed using CCK-8, Matrigel transwell, Western blot, and immunofluorescence assays in vitro, and by conducting subcutaneous xenograft experiments in mouse. The underlying mechanisms were explored using bioinformatics analysis, RNA pull-down experiments, and RNA immunoprecipitation. High expression of hsa_circ_0081111 was observed in NSCLC tissues and cell lines. This was positively correlated with the TNM stage and lymph node metastasis of NSCLC patients. Hsa_circ_0081111 overexpression promoted the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of NSCLC cells. Conversely, its downregulation showed the opposite effects. In vivo studies revealed that silencing hsa_circ_0081111 inhibited tumor growth, EMT, and MMP9 expression in tumor tissues. Mechanically, hsa_circ_0081111 enhanced Slug mRNA stability by interacting with the RNA-binding protein IGF2BP2. Taken together, hsa_circ_0081111 is an oncogenic circRNA that promotes NSCLC malignancy by regulating IGF2BP2-mediated Slug mRNA stability. Hsa_circ_0081111 has the potential to be a diagnostic and therapeutic target for NSCLC.
先前的研究表明circCOL1A2在多种癌症中具有致癌作用，如舌鳞状细胞癌、胃癌和结直肠癌。遗憾的是，circCOL1A2在肺癌（全球发病率和死亡率最高的疾病，85%的病例为非小细胞肺癌（NSCLC））中的功能和机制仍 largely未被探索。Hsa_circ_0081111（circCOL1A2）是从基因表达综合数据库（GEO）的GSE236879数据集中鉴定出来的。其表达在37对NSCLC患者的癌组织和癌旁正常组织样本以及细胞系中得到验证。通过体外CCK-8、基质胶Transwell、蛋白质免疫印迹和免疫荧光分析以及在小鼠中进行皮下异种移植实验来分析hsa_circ_0081111的功能。使用生物信息学分析、RNA下拉实验和RNA免疫沉淀来探索潜在机制。在NSCLC组织和细胞系中观察到hsa_circ_0081111的高表达。这与NSCLC患者的TNM分期和淋巴结转移呈正相关。Hsa_circ_0081111过表达促进了NSCLC细胞的增殖、侵袭和上皮-间质转化（EMT）。相反，其下调则显示出相反的效果。体内研究表明，沉默hsa_circ_0081111可抑制肿瘤组织中的肿瘤生长、EMT和MMP9表达。机制上，hsa_circ_0081111通过与RNA结合蛋白IGF2BP2相互作用增强了Slug mRNA的稳定性。综上所述，hsa_circ_0081111是一种致癌性环状RNA，通过调节IGF2BP2介导的Slug mRNA稳定性促进NSCLC的恶性发展。Hsa_circ_0081111有潜力成为NSCLC的诊断和治疗靶点。
