Circular RNA circFOXO3 regulates KDM2A by targeting miR‐214 to promote tumor growth and metastasis in oral squamous cell carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) is a pathological type of oral cancer, which accounts for over 90% of oral cancers. It has been widely shown that circRNA is involved in the regulation of multiple malignant oral diseases including OSCC. However, the mechanism underlying how circRNA regulates OSCC is still not clearly elucidated. In this article, we report circFOXO3 promotes tumor growth and invasion of OSCC by targeting miR‐214 which specifically degrades the lysine demethylase 2A (KDM2A). CircRNA sequencing was conducted in OSCC tumor and tumor‐side tissues, and the expression of circFOXO3 is found to be markedly increased in tumor tissues. CircFOXO3 is also highly expressed in several OSCC cell lines compared with human oral keratinocytes. Transwell assay and colony formation showed that knockdown of circFOXO3 prevents the invasion and proliferation of oral cancer cells. Via bioinformatic research, miR‐214 was found to be the target of circFOXO3 and correlate well with circFOXO3 both in vitro and in vivo. KDM2A was then validated by database analysis and luciferase assay to be the direct target of miR‐214. KDM2A helps to promote tumor invasiveness and proliferation of OSCC. Collectively, our results proved that circFOXO3 sponges miR‐214 to up‐regulate the expression of KDM2A, thus promotes tumor progression in OSCC.

circRNA Expression Pattern and circRNA–miRNA–mRNA Network in HCs, HSCs, and KCs of Murine Liver After Echinococcus multilocularis Infection

“…circRNAs, as the sponges of miRNAs, play the key role in different biological processes by inhibiting miRNA expression ( 17 ). To fully understand the potential mechanism of circRNAs, we predicted the target miRNAs interacting with some DECs based on miRanda and starBase databases.…”

Circular RNAs and Drug Resistance in Genitourinary Cancers: A Literature Review

“…CircFoxo3 is composed of the second exon of the FOXO3 gene containing 1435 nucleotides and it displays high conservation levels between humans and mice [ 119 ]. It is also involved in the progression of cancers including glioblastoma [ 120 ], gastric carcinoma [ 121 ], oral and esophageal squamous cell carcinoma [ 122 , 123 ], and BCa [ 124 , 125 ]. Particularly, circFoxo3 expression was increased in adriamycin-resistant hepatocellular carcinoma tissues and cell lines, and its overexpression enhances hepatocellular carcinoma invasion and growth via the miR-199a-5p/ATP Binding Cassette Subfamily C Member 1 (ABCC1) axis [ 126 ].…”

Direct Interaction of miRNA and circRNA with the Oncosuppressor p53: An Intriguing Perspective in Cancer Research

“…On the other hand, circFOXO3 is widely expressed in a series of malignant tumors, e.g., it is upregulated in prostate cancer and in hepatocarcinoma [ 109 , 110 ]. As with other circRNAs, circFOXO3 acts as a miRNA sponge with the capability to adsorb multiple miRNAs (such as miR29a-3p, miR138-5p and miR214), thus regulating the expression of downstream genes and cancer progression [ 107 , 111 ].…”