Circular RNA circZFR promotes tumorigenic capacity of lung cancer via CCND1

Abstract

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.

Prognostic and clinicopathologic significance of circZFR in multiple human cancers

“…Only one study showed the function of circZFR in hepatic carcinoma cells-derived exosome suppressing migration and invasion [26]. Only a few studies reported circZFR promoted cancers via interacting with RBPs[28] or regulating the chromatin modi cation at the transcription start site of genes [27]. More studies are needed to put into circZFR regulation mechanism.…”

“…Moreover, circZFR can bind to the cellular protein directly and interfere its function. It has been reported that circZFR decreased H3K4me3 levels on the CCND1 promoter to promote the tumorigenic capacity in LC [27]. Besides, circZFR bound with SSBP1, thereby inducing the assembly of CDK2/cyclin E1 complexes, which induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation in cervical cancer [28].…”

Prognostic and clinicopathologic significance of circZFR in multiple human cancers

“…Only one study showed the function of circZFR in hepatic carcinoma cells-derived exosome suppressing migration and invasion [26]. Only a few studies reported circZFR promoted cancers via interacting with RBPs [35] or regulating the chromatin modification at the transcription start site of genes [34]. More studies are needed to put into circZFR regulation mechanism.…”

“…Moreover, circZFR can bind to the cellular protein directly and interfere its function. It has been reported that circZFR decreased H3K4me3 levels on the CCND1 promoter to promote the tumorigenic capacity in LC [34]. Besides, circZFR bound with SSBP1, thereby inducing the assembly of CDK2/cyclin E1 complexes, which induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation in cervical cancer [35].…”