Circ_0028007 Aggravates the Malignancy of Nasopharyngeal Carcinoma by Regulating miR-656-3p/ELF2 Axis

Abstract

Circular RNAs function as important regulators in the pathogenesis of human cancers, including nasopharyngeal carcinoma (NPC). We aimed to explore the functions of circ_0028007 in NPC development. Quantitative real-time polymerase chain reaction assay was employed for the levels of circ_0028007, NUAK family kinase 1, microRNA-656-3p (miR-656-3p), and E74 like ETS transcription factor 2 (ELF2). RNase R assay was used to verify the feature of circ_0028007. Cell Counting Kit-8 assay and colony formation assay were performed to assess cell growth. Wound-healing assay and transwell assay were adopted to analyze cell migration and invasion. Tube formation assay was conducted for cell angiogenic capacity. Flow cytometry analysis was performed for cell apoptosis. Western blot assay was conducted for protein levels. Compared to normal tissues and cells, circ_0028007 level was elevated in NPC tissues and cells. Knockdown of circ_0028007 repressed NPC cell growth, migration, invasion, and angiogenesis, facilitated apoptosis in vitro and blocked tumor growth in vivo. Moreover, circ_0028007 silencing could regulate the AMP-activated protein kinase/mammalian target of rapamycin pathway in NPC cells. Circ_0028007 promoted the malignant behaviors of NPC cells via acting as miR-656-3p sponge. In addition, ELF2 was demonstrated to be the target gene of miR-656-3p. MiR-656-3p overexpression restrained NPC cell malignant phenotypes, while ELF2 elevation reversed the effects. Circ_0028007 contributed to the progression of NPC by decoying miR-656-3p and elevating ELF2. The findings might provide potential targets for NPC therapy.

Keywords: ELF2; NPC; circ_0028007; miR-656-3p.