Increased expression of Lin28B associates with poor prognosis in patients with oral squamous cell carcinoma

• Published in: PloS one Vol. 8; no. 12; p. e83869
• Main Authors: Wu, Tianfu, Jia, Jun, Xiong, Xuepeng, He, Haijun, Bu, Linlin, Zhao, Zhili, Huang, Congfa, Zhang, Wenfeng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.12.2013; Public Library of Science (PLoS)
• Subjects: Angiogenesis; Animal models; Animals; Apoptosis; Breast cancer; Caenorhabditis elegans; Cancer; Carcinoma, Squamous Cell - diagnosis; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - surgery; Cell culture; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Education; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genomes; Growth factors; Health aspects; Homology; Humans; Immunofluorescence; Immunohistochemistry; Interleukin 6; Kaplan-Meier Estimate; Laboratories; Male; Medical prognosis; Medicine; Mice; Middle Aged; miRNA; Mouth Neoplasms - diagnosis; Mouth Neoplasms - genetics; Mouth Neoplasms - pathology; Mouth Neoplasms - surgery; Multivariate analysis; Neoplasm Invasiveness; Oncology; Oral cancer; Oral squamous cell carcinoma; Patients; Prognosis; Regression analysis; Regression models; RNA-Binding Proteins - genetics; Sarcoma; Science; Squamous cell carcinoma; Stem cells; Surgery; Survival; Survivin; Tumors; Vascular endothelial growth factor; Xenografts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0083869

Recent studies showed that incomplete cell reprogramming can transform cells into tumour-like cells. Lin28A is associated with fibroblast and sarcoma cell reprogramming, whereas its homologue Lin28B is associated with hematopoietic cell reprogramming. This study aimed to investigate the expression and prognostic difference between Lin28A and Lin28B in oral squamous cell carcinoma (OSCC). Expression level was assessed by immunohistochemistry and staining location was confirmed by immunofluorescence. Prognostic values were analysed and compared by the Kaplan-Meier analysis and uni and multivariate Cox regression models. Besides, in vitro cell assays and in vivo nude mice xenograft were used to demonstrate the influence of increased Lin28B expression in OSCC. Lin28A and Lin28B expression increased in OSCC, and co-expression of Lin28A and Lin28B showed no significant association with patient prognosis. Kaplan-Meier analysis showed that patients with high Lin28B but not Lin28A expression had lower overall survival (OS) rates than those with low Lin28B expression. Further Univariate analysis showed that patients with increased Lin28B expression had shorter disease-free survival (DFS) and shorter OS, while multivariate analysis showed Lin28B overexpression with TNM stage predicted poor prognosis in patients with OSCC. Besides, stable expressing Lin28B in oral cancer cells promoted cell migration, invasion, colony formation, in vivo proliferation and increased the expression of cancer suppressor miRNA let-7 targeted genes IL-6, HMGA2, the EMT markers Snail and Twist, the angiogenesis inducer VEGF, and the apoptosis inhibitor Survivin. These combined results indicate that Lin28B is a novel marker for predicting prognosis in patients with OSCC and may be a therapeutic target.