Abstract
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.
Highlights
Oral squamous cell carcinoma (OSCC) is a morbid and frequently lethal malignancy, which has become an increasingly serious problem in South and Southeast Asia
Recent studies show that Lin28A is a reprogramming factor in induced pluripotent stem cells [29], and it is required during primordial germ cell development but its level significantly decreases with the onset of meiotic germ cell differentiation [30]
We found increased expression levels of Lin28A and its paralogous protein Lin28B in OSCCs, and that Lin28B overexpression was associated with poor overall survival (OS) of patients, which was further confirmed by in vivo and in vitro assays
Summary
Oral squamous cell carcinoma (OSCC) is a morbid and frequently lethal malignancy, which has become an increasingly serious problem in South and Southeast Asia. There are approximately 275,000 new diagnoses of OSCC annually in the world [1]. Epidemic carcinogenic risk factors, such as tobacco, betel quid consumption and epigenetic gene mutation, including TP53, PETN and NOTCH1, have been identified to be associated with OSCC [2,3]. Lin (hereinafter Lin28A) and Lin28B are two Caenorhabditis elegans lin-28 homologous proteins that the mammalian genome encodes. They share similar structures but show different functions in mRNA and miRNA regulation in mammalian cells [4,5]. Lin28A suppresses let-7 biogenesis in the cytoplasm by recruiting
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