Upregulation of XRN2 acts as an oncogene in oral squamous cell carcinoma and correlates with poor prognosis

Abstract

Backgroud: The 5'-3' exoribonuclease 2 (XRN2) has been reported involved in several tumors. However, the clinical significance and molecular mechanism of XRN2 in oral squamous cell carcinoma (OSCC) have not been elucidated.

Materials and methods: Immunohistochemistry (IHC) was used to investigate the expression of XRN2 in OSCC and adjacent noncancerous tissues, which was further identified by western blot and GEPIA2 database analysis. Moreover, the relationship between XRN2 expression and the clinicopathological characteristics and prognosis of OSCC patients was evaluated. In addition, in vitro, the effects of XRN2 on OSCC cells were evaluated by Cell Counting Kit-8 (CCK8) assay, colony formation assay, apoptosis assay, wound healing assay, and transwell assays.

Results: XRN2 was overexpressed in 44 of 77 (57.1 %) OSCC tissues. High expression of XRN2 was significantly associated with tumor differentiation (P=0.003), pathological clinical stage (P=0.045), lymph node metastasis (P=0.041), and poor overall survival (P=0.0013). Furthermore, the multivariate analysis suggested that XRN2 expression(P=0.002) was determined as an independent prognostic factor for patients with OSCC. Additionally, with functional assays in vitro, we found that downregulation of XRN2 inhibited cell proliferation, migration, and invasion, while promoted apoptosis of OSCC cells. Furthermore, knockdown of XRN2 in OSCC cells could increase the expression of E-cadherin but reduce the expression of Vimentin, which changes the characteristic of epithelial-mesenchymal transition (EMT).

Conclusion: XRN2 is significantly overexpressed in OSCC tissues and its upregulation was closely associated with poor prognosis of OSCC patients. XRN2 could be a useful prognostic biomarker and a potential therapeutic target for OSCC.

Keywords: Metastasis; Oral squamous cell carcinoma; Prognosis; Progression; XRN2.