MUC 21 is downregulated in oral squamous cell carcinoma and associated with poor prognosis

Background Mucins are usually associated with more aggressive tumor behavior and poorer clinical outcomes. However, MUC21 has never been studied in oral squamous cell carcinoma (OSCC). MUC21 has been observed to contribute to the anti-adhesion effects of cancer cells in vitro. It might serve as an important molecule in OSCC. Methods Our microarray data based on 10 oral squamous cell carcinoma (OSCC) and paired adjacent normal tissue (para-OSCC), and similar data sets from GEO and TCGA RNAseq data were analyzed to screen out the differentially expressed genes including MUC21. RT-PCR analysis was carried out to further confirm the alteration of MUC21 and the epithelial differentiation related co-expressed genes in OSCC. Then, the relationship of MUC21 changes in OSCC with the corresponding clinical characteristics and outcomes was investigated using immunohistochemistry (IHC) on other 102 paired samples of OSCC and para-OSCC. OSCC cell lines SCC15 and HSC-3 with MUC21 overexpression or knockdown were studied in vitro through CCK8, Annexin V/PI assays, wound healing, and Transwell experiments. Results MUC21 was significantly downregulated in OSCC compared with normal oral tissue, as evidenced by high throughput gene expression datasets, RT-PCR and immunohistochemistry analysis. Additionally, 11 genes co-expressed with MUC21 were revealed. Among them, the mucosae differentiation related KRT4, KRT13, and CRNN were further confirmed by RT-PCR and IHC. The downregulation of MUC21 was associated with pathological lymph node metastasis, poorer tumor differentiation, and shorter survival rates. However, hardly no statistically significant changes were detected in CCK8 analysis, Annexin V/PI assays, wound healing, and Transwell experiments on the OSCC cell lines with MUC21 overexpression or knockdown. Conclusion Low MUC21 expression in OSCC is associated with less epithelial differentiation, more clinical aggressiveness and worse prognosis. MUC21 could serve as a new prognostic marker in OSCC, though it might not be a driver oncogene.