Circular RNAs (CircRNAs) are a group of noncoding RNAs that have essential function in the development and progression of various cancers. The expression pattern and function of circRNA in lung cancer is not fully understood. In the present study, we aimed to investigate the expression profiles and underlying mechanism of circRNA circ_POLA2 in lung cancer cell stemness. Circ_POLA2 was highly expressed in lung cancer tissues and predicted a poor prognosis in lung cancer patients. Knockdown of circ_POLA2 inhibited the stemness of lung cancer cells, which is evident by the decreased sphere‐formation ability, ALDH1 activity, and stemness marker expression, but had no effects on cell viability. Mechanistically, circ_POLA2 functioned as a ceRNA by sponging miR‐326. Furthermore, miR‐326 negatively regulated G protein subunit beta 1 (GNB1) expression by targeting its 3′‐UTR (untranslated region). Intriguingly, we found that GNB1 was overexpressed and associated with poor prognosis in lung cancer patients. Overexpression of GNB1 could antagonize the inhibitory effect of circ_POLA2 knockdown on lung cancer cell stemness. In conclusion, circ_POLA2 promotes lung cancer cell stemness and progression via regulating the miR‐326/GNB1 axis, which might serve as a novel therapeutic target for lung cancer patients.

中文翻译：

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circRNA circ_POLA2通过调节miR-326/GNB1轴促进肺癌细胞干细胞

环状 RNA (CircRNAs) 是一组非编码 RNA，在各种癌症的发展和进展中具有重要作用。circRNA 在肺癌中的表达模式和功能尚不完全清楚。在本研究中，我们旨在研究 circRNA circ_POLA2 在肺癌细胞干细胞中的表达谱和潜在机制。Circ_POLA2在肺癌组织中高表达，预测肺癌患者预后不良。circ_POLA2 的敲低抑制了肺癌细胞的干性，这通过降低的球形成能力、ALDH1 活性和干性标记表达来证明，但对细胞活力没有影响。从机制上讲，circ_POLA2 通过海绵 miR-326 发挥 ceRNA 的作用。此外，miR-326 通过靶向其 3'-UTR（非翻译区）负调节 G 蛋白亚基β1（GNB1）的表达。有趣的是，我们发现 GNB1 过度表达并与肺癌患者的不良预后相关。GNB1的过表达可以拮抗circ_POLA2敲低对肺癌细胞干细胞的抑制作用。总之，circ_POLA2通过调节miR-326/GNB1轴促进肺癌细胞干性和进展，这可能成为肺癌患者的新治疗靶点。