Circ_0089823 reinforces malignant behaviors of non-small cell lung cancer by acting as a sponge for microRNAs targeting SOX4,

Abstract

In recent years, increasing evidence indicates the significant roles of circRNAs in carcinogenesis. However, their roles in lung cancer remain largely unclear. We profiled the circRNA expression in 10 paired non-small cell lung cancer (NSCLC) and adjacent non-cancer tissues using high-throughput sequencing. A total of 183 up-regulated and 428 down-regulated circRNAs were identified in the NSCLC tissues (fold change ≥ 2, P < 0.05). Circ_0089823, an up-regulated circRNA (5.4-fold, P = 0.0017), was further investigated through loss-of-function and gain-of-function. The circ_0089823 level in NSCLC samples was related to the gender, tumor size, pathological type, TNM stage and smoking history. Knockdown of circ_0089823 suppressed cell proliferation, induced cell cycle arrest and apoptosis of NSCLC cells in vitro. Additionally, circ_0089823-silenced xenografts grew much slowly. On the contrary, its over-expression promoted the malignant behaviors of NSCLC cells. Furthermore, SOX4, a tumor-promoting transcription factor, was highly expressed in NSCLC tissues and positively regulated by circ_0089823. Bioinformatic analysis revealed several potential binding sites for miR-507, miR-557, miR-579-3p and miR-1287-5p in circ_0089823 and SOX4 3′-untranslated region, which was later confirmed by luciferase reporter assay. Interestingly, silencing SOX4 countervailed the effects of circ_0089823 over-expression on NSCLC cells. Here, we revealed that circ_0089823 might act as a sponge of microRNAs targeting SOX4, thus increasing the expression of SOX4, thereby reinforcing the malignant behaviors of NSCLC cells. This study indicates that circ_0089823 has the potential to become a candidate target for NSCLC treatment.

Keywords

• Circ_0089823
• Non-small cell lung cancer
• Proliferation
• Apoptosis
• SOX4
• MicroRNA