The potential mechanism of WT1-associated protein-induced N-6-methyladenosine modification of colony-stimulating factor 2 in the progression of oral squamous cell carcinoma by JAK/STAT3 pathway regulation.

Abstract

Colony-stimulating factor 2 (CSF2) plays a regulatory role in numerous cancers. However, there is needed to investigate the role of CSF2 in oral squamous cell carcinoma (OSCC) malignant phenotype and the specific mechanisms of CSF2 N-6-methyladenosine (m6A) modification. Therefore, we investigated the regulatory mechanism of m6A-modified CSF2 by WT1-associated protein (WTAP) in OSCC via qRT-PCR, western blot, WTAP and CSF2 overexpression in OSCC. In a panel of OSCCs, Kaplan-Meier plot analysis indicated that high expression of CSF2 was associated with poorer prognosis. Cell functional experiments revealed that enrichment of CSF2 promoted the proliferation and migration of OSCC cells by activating the JAK/STAT3 pathway, whereas the reduced expression of CSF2 resulted in the malignant decline of OSCC cells by blocking the JAK/STAT3 pathway. This study also confirmed that WTAP enhanced the m6A level of CSF2 and facilitated the expression of CSF2 and that CSF2 silencing blocked the invasive phenotype of OSCC cells and reversed the malignancy induced by WTAP overexpression. Overall, this study demonstrated that WTAP mediates the m6A modification of CSF2 and the JAK/STAT3 pathway, which plays an oncogenic role in the development of OSCC and can be a target for the treatment of patients with OSCC.