Microfibrillar-associated protein-2 facilitates aggressive progression of oral squamous cell carcinoma cells through Kelch-like E3 ubiquitin ligase-associated protein 1/nuclear factor erythroid 2-related factor 2 signaling pathway.

Abstract

Objective: This study aims to explore the role of microfibrillar-associated protein-2 (MFAP2) in oral squamous cell carcinoma (OSCC).

Material and methods: Analysis of MFAP2 expression in diverse cancers and its relationship with head-and-neck squamous cell carcinoma (HNSC) prognosis. MFAP2 abundance was identified in OSCC cells and in human oral epithelial cells using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays. Knockdown and overexpression techniques were utilized to examine the mechanism by which MFAP2 and nuclear factor erythroid 2-related factor 2 (NRF2) affect OSCC malignancy. Cell viability, proliferation, and apoptosis were assessed using cell counting kit-8, colony formation, flow cytometry, wound healing, and Transwell tests. Messenger ribonucleic acid expression was detected using qRT-PCR, whereas protein level was analyzed using Western blot.

Results: MFAP2 and Kelch-like E3 ubiquitin ligase (ECH)-associated protein 1 (KEAP1) had high expression levels in numerous tumors, including OSCC, and the high expression level of MFAP2 was associated with unfavorable HNSC outcomes. MFAP2 was abundantly expressed in five OSCC cell lines, with the peak expression observed in squamous cell carcinoma (SCC)-15 and SCC-9 cells, making them suitable for subsequent studies. MFAP2 knockdown hindered the proliferative and mobile capacity of OSCC cells, yet it supported cell apoptosis. MFAP2 silencing led to a notable drop in KEAP1 and NRF2 expression levels in OSCC cells. NRF2 overexpression could counteract the effects of MFAP2 knockout, which included diminished proliferation and movement and heightened apoptosis in OSCC cells.

Conclusion: The results of this study indicated that MFAP2 facilitated the malignant progression of OSCC and provided insights into the downstream regulatory mechanism of the KEAP1/NRF2 axis, highlighting the potential application of MFAP2 in OSCC management.