Background. Circular RNAs (circRNAs) are powerful factors in regulating various cancer behaviors. It has been manifested in previous researches that circular RNA hsa_circ_0005909 (circ_0005909) exhibits a regulatory function in osteosarcoma. However, there are no other studies on whether circ_0005909 displays potential functions on the progression of non-small-cell lung cancer (NSCLC). Methods. RT-PCR was applied to examine the expression of circ_0005909 in NSCLC. To study the specific behaviors of NSCLC cells after circ_0005909 knockdown, cell counting kit-8 (CCK-8) assays, colony formation assays, Transwell assays, and xenograft tumor model assays were conducted. Bioinformatics and luciferase reporter assays were employed to study the association among circ_0005909, miRNA-338-3p, and SOX4. Results. In this research, our group firstly showed that circ_0005909 expressions were distinctly increased in NSCLC specimens and cell lines. Clinical studies revealed that high circ_0005909 expressions were associated with poor prognosis of NSCLC patients. Functionally, knockdown of circ_0005909 was observed to suppress the proliferation, metastasis, and drug resistance of NSCLC cells. In the terms of mechanism, circ_0005909 could act as a sponge of miRNA-338-3p, and miRNA-338-3p could target SOX4. In addition, miRNA-338-3p inhibitors reversed the suppressor ability of circ_0005909 silence on NSCLC behaviors. Conclusions. circ_0005909 promoted the progression of NSCLC via the modulation of the miRNA-338-3p/SOX4 axis, which may be a therapeutic target for NSCLC.

中文翻译：

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circRNA hsa_circ_0005909 通过 miRNA-338-3p/SOX4 通路预测非小细胞肺癌的不良预后并促进其生长、转移和耐药性

背景。环状 RNA (circRNA) 是调节各种癌症行为的有力因素。以往的研究表明，环状RNA hsa_circ_0005909（circ_0005909）在骨肉瘤中具有调节作用。然而，关于 circ_0005909 是否在非小细胞肺癌 (NSCLC) 的进展中表现出潜在功能，尚无其他研究。方法。应用 RT-PCR 检测 circ_0005909 在 NSCLC 中的表达。为了研究 circ_0005909 敲低后 NSCLC 细胞的特定行为，进行了细胞计数 kit-8 (CCK-8) 测定、集落形成测定、Transwell 测定和异种移植肿瘤模型测定。采用生物信息学和荧光素酶报告基因分析来研究 circ_0005909、miRNA-338-3p 和 SOX4 之间的关联。结果。在这项研究中，我们组首次发现circ_0005909在NSCLC标本和细胞系中的表达明显增加。临床研究表明，circ_0005909 的高表达与 NSCLC 患者的不良预后相关。在功能上，观察到 circ_0005909 的敲低可抑制 NSCLC 细胞的增殖、转移和耐药性。在机制上，circ_0005909可以作为miRNA-338-3p的海绵，miRNA-338-3p可以靶向SOX4。此外，miRNA-338-3p 抑制剂逆转了 circ_0005909 沉默对 NSCLC 行为的抑制能力。结论。circ_0005909通过调节miRNA-338-3p/SOX4轴促进NSCLC的进展，这可能是NSCLC的治疗靶点。