AUTHOR=Lan Ting , Ge Qi , Zheng Ke , Huang Li , Yan Yuxiang , Zheng Lixin , Lu Youguang , Zheng Dali 

TITLE=FAT1 Upregulates in Oral Squamous Cell Carcinoma and Promotes Cell Proliferation via Cell Cycle and DNA Repair

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.870055

DOI=10.3389/fonc.2022.870055

ISSN=2234-943X

ABSTRACT=Objective: Previous studies have revealed FAT atypical cadherin 1 (FAT1) plays a tumor suppressive or oncogenic role in a context-dependent manner in various cancers. However, the functions of FAT1 are ambiguous in tumorigenesis owing to inconsistent research in oral squamous cell carcinoma (OSCC). The present study aimed to gain an insight into the role of FAT1 in the tumor genesis and development.
Methods: The expression, mutant and survival data analysis were done using data from the Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database, verified with clinical samples via real-time polymerase chain reaction (qRT-PCR), western blot (WB) and immunohistochemical (IHC) staining. OSCC cells transfected with siRNA was employed for in vitro assessment in cell proliferation, apoptosis, migration ability in appropriate ways. The underlying mechanism was explored by RNA-sequencing after FAT1 silencing.
Results: Overall, FAT1 significantly raised in OSCC with a poor prognosis outcome. The in vitro experiment showed the promoting effect of FAT1 in the proliferation and migration of OSCC cells. FAT1 can also inhibit both the early and late apoptosis of OSCC cells. RNA-sequencing analysis of FAT1 silencing revealed that the cell cycle, DNA replication, and some core genes (MCM2, MCM5, CCNE1 SPC24, MYBL2, KIF2C) may be the potential mechanism in OSCC. 
Conclusions: FAT1 may act as oncogenesis in OSCC with potential mechanism influencing the cell cycle and DNA repair.