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

Molecular Medicine

Huangxing Mao¹  Hailin Zhang¹  Zan Li¹  Anji Xu¹  Haolei Tan¹  Ying Liu²  Hui Wang³  Huayi Ren⁴  Xiao Zhou⁵  Bo Zhou⁵  Mingjing Peng⁶  Ying Long⁶  Yue Zhou⁶ 

[1] Department of Head and Neck Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410013, Changsha, Hunan, People’s Republic of China;Hunan Provincial Clinical Research Centre for Oncoplastic Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410013, Changsha, Hunan, People’s Republic of China;Hunan Traditional Chinese Medical College, 412012, Zhuzhou, Hunan, People’s Republic of China;Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410013, Changsha, Hunan, People’s Republic of China;Translational Medicine Centre, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, 410013, Changsha, Hunan, People’s Republic of China;Translational Medicine Centre, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, 410013, Changsha, Hunan, People’s Republic of China;Department of Head and Neck Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410013, Changsha, Hunan, People’s Republic of China;Hunan Provincial Clinical Research Centre for Oncoplastic Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410013, Changsha, Hunan, People’s Republic of China;Translational Medicine Centre, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, 410013, Changsha, Hunan, People’s Republic of China;Hunan Provincial Clinical Research Centre for Oncoplastic Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410013, Changsha, Hunan, People’s Republic of China;Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410013, Changsha, Hunan, People’s Republic of China;

关键词: CASC18;    TGFB2;    ceRNA;    Occult lymph node metastasis;    Tongue squamous cell carcinoma;   

DOI  :  10.1186/s10020-021-00345-9

来源: Springer

【 摘 要 】

BackgroundTongue 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.MethodsIn 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.ResultsCASC18 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.ConclusionIn 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.

【 授权许可】

CC BY