Association of CASC18/miR-20a-3p/TGFB2 ceRNA axis with occult lymph node metastasis in tongue squamous cell carcinoma

• Published in: Molecular medicine (Cambridge, Mass.) Mass.), 2021-08, Vol.27 (1), p.85-13, Article 85
• Main Authors: Zhou, Bo, Zhou, Yue, Liu, Ying, Zhang, Hailin, Mao, Huangxing, Peng, Mingjing, Xu, Anji, Li, Zan, Wang, Hui, Tan, Haolei, Ren, Huayi, Zhou, Xiao, Long, Ying
• Format: Article
• Language: English
• Subjects: Adult; Aged; Carcinoma, Squamous Cell - etiology; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; CASC18; Cell Line, Tumor; ceRNA; Computational Biology - methods; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Lymphatic Metastasis; Male; MicroRNAs - genetics; Middle Aged; Models, Biological; Neoplasm Grading; Neoplasm Staging; Occult lymph node metastasis; RNA, Long Noncoding - genetics; TGFB2; Tongue Neoplasms - etiology; Tongue Neoplasms - metabolism; Tongue Neoplasms - pathology; Tongue squamous cell carcinoma; Transforming Growth Factor beta2 - genetics; Workflow
• ISSN: 1076-1551; 1528-3658
• DOI: 10.1186/s10020-021-00345-9

Tongue squamous cell carcinoma (TSCC) ranks as the most prevalent malignancy in the oral cavity. TSCC patients with occult lymph node metastasis (OLNM) are thought to be at risk of worse outcome. However, regulatory mechanisms underlying OLNM remain less investigated. In the present study, CASC18/miR-20a-3p/TGFB2 axis was identified and evaluated by bioinformatic and qRT-PCR analyses. Effects of CASC18 knockdown on cell migration and invasion were determined by wound healing and transwell assays. Western blot, ELISA, RNA pulldown and luciferase reporter assays were performed for mechanism verification. CASC18 was identified up-regulating in TSCC tumours, and especially in those from patients with OLNM. Importantly, we found higher CASC18 expression was positively correlated with the presence of OLNM and worse outcome of TSCC patients. Furthermore, we demonstrated that CASC18 knockdown repressed cell migration and invasion through inhibiting epithelial-mesenchymal transition, which could be partly rescued by miR-20a-3p inhibitor. Regarding the molecular mechanism, we further confirmed that CASC18 functioned as a ceRNA to sponge miR-20a-3p to enhanceTGFB2 expression and secretion. In conclusion, we have reported a novel CASC18/miR-20a-3p/TGFB2 ceRNA axis in OLNM of TSCC. Our findings will contribute to a deeper understanding of the molecular mechanism of OLNM in TSCC, and facilitate the development of diagnostic methods for assisting treatment decision-making.