MAL suppresses OSCC tumorigenesis by maintaining epithelial cell differentiation [article]

Wantao Chen, Xueqin Zhu, Zheqi Liu, Shengcai Qi, Xin Zou, Tingwei Lu, Xing Ke, Xing Qin, Xiaoning Wang, Ming Yan, Qin Xu, Jianjun Zhang (+4 others)
2021 bioRxiv   pre-print
Oral squamous cell carcinoma (OSCC) is widely recognized as an optimal model for precise medicine guided molecular biomarkers of cancer, however, few clinical practices were applied till now. Based on the data from our own studies and published papers, it was found that the expression of MAL was significantly decreased in epithelial cancer as compared with normal tissues, and exhibited a opposite association with pathological grade. To study the molecular events related to deficiency of MAL
more » ... ng carcinogenesis, occurrence and development, a Mal knockout mouse model was constructed and consistently reproduced and bred. The Mal knockout mice are highly vulnerable to tumor induction by carcinogen of 4NQO, evidenced by their extremely earlier carcinogenesis, higher incidence, and more aggressive growth. Analysis of scRNA-seq data indicated that Mal knockout mice lost the ability in maintaining epithelial cell differentiation and get more prone to carcinogen with a remarkably higher incidence of epithelial malignancy. Further analyses identified putative co-functional genes of MAL, including DSG1, AQP3 and S100A8, which are key factors in maintaining epithelial cell differentiation. To conclude, the current study exhibits the clinical significance and explains the tumor suppressing function of MAL. The results also suggest the potential of MAL and its co-functional genes being biomarkers for designing the prevention and/or differentiation therapy strategies in OSCC.
doi:10.1101/2021.12.01.470749 fatcat:fr6wkd4v7jaqtd4tm4jsdjzcne