Mechanism Of WNT7B-Mediated Canonical Wnt Pathway In The Development Of Oral Cancer

Oral cancer and head and neck tumors are the sixth most common cancers in the world,and oral squamous cell carcinomas(OSCC)is the main type with a low five-year survival rate.In the special open environment of the mouth,the occurrence of oral cancer is regulated by endogenous and external environmental factors.Clarifying the molecular mechanisms that regulate the occurrence and development of oral cancer will help to better analyze the causes of the disease,design more effective solutions for the diagnosis and treatment of the disease,and also help to provide new targets for drug development.Our earlier research has found that the Wnt signaling pathway may be related to the development of OSCC.The WNT pathway is widely involved in the development of the body and the development of diseases,including tumors,and can usually be divided into Wnt/?-catenin,also called the classic Wnt signaling pathway,the Vt-PCP pathway,and the Wnt-calcium signaling pathway.This study focused on whether two important ligand proteins,WNT7 B and WNT5 A,were involved in the development of oral cancer through the Wnt/?-catenin pathway in OSCC.By analyzing sequencing data from existing patient tissue and oral cancer patients downloaded from GEO databases,we found that WNT7 B and WNT5 A had varying degrees of expression in oral cancer in 19 human WNT ligands.The validation of clinical patients and OSCC tumor cells showed that WNT7 B mRNA and protein were synchronized rise in patients and tumor cell lines,while WNT5 A was highly expressed in clinical samples,but low expression in two OSCC cell lines,SCC9 and FaDu,indicating that their expression was heterogeneous.Then,with siRNA interference and shRNA-based lenti-virus vector stabilization system,we further explore the effects of WNT7 B on the phenotypes of cancer cells and their molecular machanism.The results showed that the degree of WNT7 B expression was not significantly correlated with cell cycle and the ability of cancer cells to multiply,and had no significant effect on some key proteins of proliferation and apoptosis signals such as CyclinD1 and BIRC5 expression,while the reduced expression of WNT7 B inhibited cell migration to some extent,and this effect could be achieved by the classical Wnt/?-catenin and the pathway regulation of some EMT-related proteins downstream,such as MMP1.With the help of WNT7 B stabilized knock-down cell lines based on slow virus,we conducted animal tumor experiments,and the results at animal levels were basically the same as in cell experiments.Based on the above results,we can initially conclude that the WNT signaling pathway is involved in tumor progression in the development of oral cancer,and its mechanism of action may be achieved by changing cell attack ability through WNT7 B and its downstream signaling molecules.