CircRNA ZNF609 Knockdown Suppresses Cell Growth via Modulating miR-188/ELF2 Axis in Nasopharyngeal Carcinoma

Circular RNAs (circRNAs) and microRNAs (miRNAs) have been reported to act as the important regulators in nasopharyngeal carcinoma (NPC). CircRNA ZNF609 (circ-ANF609) and miR-188 have been, respectively, reported to play a pro-cancer and anti-cancer role in NPC. The purpose of this study is to reveal the functional relation of circ-ZNF609 and miR-188 in NPC development.

The transcription level and protein level of genes were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assay, respectively. Cell proliferation was analyzed using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Furthermore, flow cytometry analysis was used to assess cell cycle transition and cell apoptosis rate. Besides, the interaction between miR-188 and circ-ZNF609 or E74-like factor 2 (ELF2) was predicted by starbase or microT-CDS, and then confirmed by the dual luciferase reporter assay and RIP assay.

Circ-ZNF609 and ELF2 levels were increased and miR-188 level was decreased in NPC. Circ-ZNF609 knockdown significantly inhibited cell proliferation and cell cycle transition, as well as accelerated apoptosis in NPC cells. Interestingly, circ-ZNF609 directly bound to miR-188. Circ-ZNF609 regulated NPC cell growth through modulating miR-188 expression. In addition, miR-188 suppressed NPC cell growth via directly targeting ELF2. Finally, we confirmed that circ-ZNF609 mediated miR-188 level to modulate ELF2 expression.

Our findings demonstrated that circ-ZNF609 depletion-repressed proliferation and cell cycle transition, and induced apoptosis of NPC cells via modulation of miR-188/ELF2 axis, providing potential targets for the therapy of NPC.