Circular RNA circZFR promotes tumorigenic capacity of lung cancer via CCND1

BACKGROUND: To explore the role of circular RNA (circRNA) circZFR in tumorigenic capacity of lung cancer (LC). METHODS: Thirty primary LC tissues were used to detect circRNAs expression. CircZFR was silenced in two LC cell lines using lentivirus-mediated short hairpins RNAs. Quantitative real time PCR (qRT-PCR), northern blot and in situ hybridization (ISH) assay were used to measure the expression of circRNA. RESULTS: CircRNA circZFR was highly expressed in LC tumors. CircZFR deficiency significantly abrogated clone formation. CircZFR depletion substantially decreased tumor growth compared to WT control cells. CircZFR overexpression was dramatically increased cell growth in LC cell lines. Consequently, circZFR overexpression substantially promoted tumor propagation. Consistently, circZFR deficiency significantly reduced the expression of CCND1 and major cell cycle genes in LC cell lines. In contrast, circZFR depletion did not alter the expression of ZFR. Consequently, circZFR deficiency dramatically decreased H3K4me3 levels on the CCND1 promoter at −1,100 to −900 bp segment of CCND1 promoter. CONCLUSIONS: CircZFR was related with LC growth in vitro and in vivo and tumorigenic capacity of LC. The possible mechanism was to regulating expression of CCND1, indicating the circZFR/CCND1 signaling might be a promising therapeutic target for LC treatment.