MiR-155-5p promotes oral cancer progression by targeting chromatin remodeling gene ARID2

Abstract

Background: Dysregulation of miRNAs is associated with aberrant migration and invasion by suppressing relevant target genes in multiple cancers, including oral squamous cell carcinoma (OSCC). Accumulating evidence suggests that microRNA-155-5p is involved in carcinogenesis and tumor progression. However, the exact function and molecular mechanism of miR-155-5p in OSCC remain unclear. This study aimed to investigate the function of miR-155-5p and the molecular mechanisms underlying the influencing progression of OSCC.

Methods: The miR-155-5p expression level in the OSCC tissues and oral cancer cell lines were determined by the qRT-PCR. Gain-of-function and knockdown approach were used to examine the effect of miR-155-5p on cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of OSCC. The luciferase reporter assay was applied to confirm the AT-rich interactive domain 2 (ARID2) as a potential target of miR-155-5p, and the rescue experiment was employed to verify the roles of the miRNA-155-5p-ARID2 axis in OSCC progression. Immunohistochemical staining was used to detect ARID2 expression in another cohort sample tissues from OSCC patients.

Results: MiR-155-5p was significantly upregulated in OSCC tissues and cell lines. The miR-155-5p expression level was positively correlated with tumor size, TNM stage, histological grade and lymph node metastasis of OSCC patients. Functional assays demonstrated that miR-155-5p enhanced OSCC cell proliferation, migration and invasion. Mechanistically, ARID2 was identified as a direct target and functional effector of miR-155-5p in OSCC. Furthermore, ARID2 overexpression could rescue the aberrant biological function by overexpressed miR-155-5p in OSCC cells. Notably, we showed that ARID2 could be used as an independent prognosis factor in OSCC.

Conclusions: Our results suggest that miR-155-5p facilitates tumor progression of OSCC by targeting ARID2, and miR-155-5p-ARID2 axis may be a potential therapeutic target of OSCC.

Keywords: AT-rich interactive domain 2; Metastasis; MiR-155-5p; Oral squamous cell carcinoma; Prognosis.