The FUS/COL11A1/ZEB1 Axis Contributes to the Development of Oral Squamous Cell Carcinoma.

Abstract

Objective: Oral squamous cell carcinoma (OSCC) is a common type of head and neck cancer with high metastasis rate and poor prognosis. This study aimed to explore the role of collagen type XI alpha 1 (COL11A1) and its detailed mechanisms in OSCC progression.

Methods: Quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis was used to measure the level of COL11A1, fused in sarcoma/translocated in liposarcoma (FUS) and zinc finger E-box binding homeobox 1 (ZEB1). The protein expression of COL11A1, E-cadherin, N-cadherin, FUS, and ZEB1 were detected using Western blot. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and 5-Ethynyl-2'-deoxyuridine (EdU) staining assays were conducted to measure cell proliferation. Cell migration and invasion were evaluated via wound-healing assay and transwell migration and invasion assays, respectively. Moreover, epithelial mesenchymal transition (EMT) was determined via detecting the expression of EMT-related proteins, including E-cadherin and N-cadherin. RNA immunoprecipitation assay was conducted to evaluate the relationship between ZEB1 and COL11A1. In vivo animal experiments were carried out to explore the role of COL11A1 in OSCC mice, and immunohistochemistry assay was performed to detect the level of ZEB1 and EMT-related proteins in tumor tissues from mice.

Results: COL11A1 was augmented in OSCC tissues and cells. COL11A1 knockdown significantly inhibited cell proliferation, migration, invasion, and EMT in OSCC cells. FUS was increased in OSCC tissues. FUS stabilized the mRNA level of COL11A1 and positively regulated the protein expression of COL11A1. ZEB1 was highly expressed in OSCC tissues, and COL11A1directly targeted ZEB1. The inhibition effects of COL11A1 knockdown on cell proliferation, invasion, migration, and EMT were reversed by ZEB1 overexpression in OSCC cells. Additionally, COL11A1 depletion markedly repressed tumor growth through decreasing ZEB1 expression in vivo.

Conclusion: FUS stabilized COL11A1 to promote the malignant progression of OSCC via regulating ZEB1 expression.