CircRNA circ_0067772 aggravates the malignant progression of cutaneous squamous cell carcinoma by regulating miR-1238-3p/FOXG1 axis.

Abstract

Cutaneous squamous cell carcinoma (CSCC) is a severe malignancy derived from skin. Dysregulated circular RNAs (circRNAs) might play vital roles in tumor development. Here, we aimed to explore the function of a novel circRNA circ_0067772 in CSCC. Quantitative real-time PCR (qRT-PCR) or Western blot assay was performed to determine the expression of circ_0067772, microRNA (miR)-1238-3p and forkhead box protein G1 (FOXG1). Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Transwell assay and wound healing assay were employed to examine cell metastasis. Flow cytometry was employed to monitor cell cycle and apoptosis. The target association between miR-1238-3p and circ_0067772 or FOXG1 was validated by dual-luciferase reporter assay. Moreover, role of circ_0067772 in vivo was investigated via xenograft model in nude mice. Circ_0067772 and FOXG1 were upregulated, while miR-1238-3p was downregulated in CSCC tissues and cells. Circ_0067772 knockdown conferred inhibitory effects on cell proliferation, migration and invasion of CSCC cells. MiR-1238-3p served as a target of circ_0067772, whose silencing could reverse circ_0067772 knockdown-induced inhibitory impact on the malignant cellular behaviors. Circ_0067772 positively regulated FOXG1 expression by antagonizing miR-1238-3p. Additionally, miR-1238-3p could repress CSCC cell proliferation, migration and invasion by targeting FOXG1. Also, circ_0067772 knockdown hindered CSCC tumor growth in vivo. Our study identified a novel oncogenic circRNA and the involvement of circ_0067772/miR-1238-3p/FOXG1 axis in CSCC development, providing a target for CSCC therapy.