Circular RNA ZFR accelerates non-small cell lung cancer progression by acting as a miR-101-3p sponge to enhance CUL4B expression

Non-small-cell lung carcinoma (NSCLC) is the most common type of lung cancer. Circular RNA ZFR (circZFR) is an identified circular RNA (circRNA) that is correlated with cancer progression. However, the role of circZFR in NSCLC remains unknown. In the present study, we aimed to investigate the function of circZFR in NSCLC and the underlying mechanism. The expression patterns of circZFR were determined using qRT-PCR in NSCLC samples and cell lines. The subcellular distribution of circZFR in NSCLC cells was analyzed by fluorescence in situ hybridization (FISH). Cell proliferation was examined utilizing the CCK-8 assay. Cell migration and invasion were evaluated using the Transwell assay. We used the bioinformatics software TargetScan and miRanda to predict circRNA–miRNA and miRNA–mRNA interactions. Our results showed that circZFR expressions were significantly upregulated in NSCLC tissues and cell lines. Knockdown of circZFR significantly inhibited the cell proliferation, migration and invasion of NSCLC cells in vitro. Furthermore, we demonstrated that circZFR acted as a sponge to absorb microRNA-101-3p (miR-101-3p) and promoted cullin 4B (CUL4B) expression. Collectively, our results demonstrated that circZFR exhibited a carcinogenic role by sponging miR-101-3p and regulating CUL4B expression in NSCLC. These findings provided evidence for understanding the role of circZFR in NSCLC tumourigenesis.

非小细胞肺癌（Non-small-cell lung carcinoma, NSCLC）是最为常见的肺癌类型。环状RNA ZFR（circZFR）是一种已被证实的环状RNA（circular RNA, circRNA），与癌症进展密切相关。然而，circZFR在非小细胞肺癌中的作用仍未明确。本研究旨在探讨circZFR在非小细胞肺癌中的功能及其潜在作用机制。我们采用实时定量逆转录聚合酶链反应（quantitative real-time reverse transcription PCR, qRT-PCR）检测非小细胞肺癌组织及细胞系中circZFR的表达模式；通过荧光原位杂交（fluorescence in situ hybridization, FISH）分析circZFR在非小细胞肺癌细胞中的亚细胞定位；利用细胞计数试剂盒-8（Cell Counting Kit-8, CCK-8）实验检测细胞增殖活性；采用Transwell实验评估细胞迁移与侵袭能力。此外，本研究借助生物信息学软件TargetScan与miRanda预测了circRNA-miRNA及miRNA-mRNA的相互作用靶点。本研究结果显示，circZFR在非小细胞肺癌组织及细胞系中的表达水平显著上调。敲低circZFR可显著抑制非小细胞肺癌细胞的体外增殖、迁移及侵袭能力。进一步研究证实，circZFR可作为分子海绵吸附微小RNA-101-3p（miR-101-3p），并上调CUL4B的表达。综上，本研究结果表明，circZFR通过吸附miR-101-3p并调控CUL4B的表达，在非小细胞肺癌中发挥致癌作用。上述研究结果为阐明circZFR在非小细胞肺癌发生发展中的作用提供了实验依据。