University of Tibetan Medicine, Lhasa, China.
Thorac Cancer. 2024 Jan;15(1):77-88. doi: 10.1111/1759-7714.15165. Epub 2023 Nov 22.
Gentiana macrophylla Pall. is a traditional Tibetan medicinal herb possessing antinociceptive and anti-inflammatory activities. Circular RNAs (circRNAs) have been identified to be involved in the tumorigenesis of non-small cell lung cancer (NSCLC). Here, this study focused on investigating the function and mechanism of Gentiana macrophylla flavonoids (GF) and circ_0059665 in NSCLC progression.
The contents of mRNA and protein were detected using qRT-PCR and western blotting analysis. Cell proliferative and invasive abilities were evaluated by cell counting kit-8, EdU, colony formation and transwell assays, respectively. M2 macrophage polarization was analyzed by flow cytometry.
GF treatment suppressed NSCLC cell proliferation, invasion and M2 macrophage polarization under hypoxic conditions. Circ_0059665 was highly expressed in NSCLC tissues and cells. Its expression was increased under hypoxic conditions but was reduced following GF treatment. Furthermore, circ_0059665 overexpression reversed the anticancer effects of GF on NSCLC cells under hypoxic conditions. Mechanistically, circ_0059665 acted as a sponge for miR-512-5p to regulate NOVA2 expression. Hypoxia decreased miR-512-5p levels, and increased NOVA2 levels in NSCLC cells, while these tendencies were abolished after GF treatment. Circ_0059665 silencing inhibited NSCLC cell proliferation, invasion and M2 macrophage polarization in hypoxic environments, which were counteracted by NOVA2 overexpression. Moreover, NOVA2 upregulation reversed the suppressive effects of GF on NSCLC cells with hypoxia treatment. In addition, GF impeded NSCLC tumor growth in vivo via suppressing circ_0059665.
GF treatment in hypoxic environments suppressed NSCLC cell proliferation, invasion and M2 macrophage polarization via the circ_0059665/miR-512-5p/NOVA2 axis.
秦艽是一种传统的藏药，具有镇痛和抗炎活性。环状 RNA（circRNAs）已被确定参与非小细胞肺癌（NSCLC）的发生。本研究重点探讨了秦艽总黄酮（GF）和 circ_0059665 在 NSCLC 进展中的作用和机制。
采用 qRT-PCR 和 Western blot 分析检测 mRNA 和蛋白含量。通过细胞计数试剂盒-8、EdU、集落形成和 Transwell 实验分别评估细胞增殖和侵袭能力。通过流式细胞术分析 M2 巨噬细胞极化。
GF 处理抑制了低氧条件下 NSCLC 细胞的增殖、侵袭和 M2 巨噬细胞极化。circ_0059665 在 NSCLC 组织和细胞中高表达。低氧条件下其表达增加，但经 GF 处理后减少。此外，circ_0059665 过表达逆转了低氧条件下 GF 对 NSCLC 细胞的抗癌作用。机制上，circ_0059665 作为 miR-512-5p 的海绵体调节 NOVA2 表达。低氧降低了 NSCLC 细胞中 miR-512-5p 的水平，增加了 NOV A2 的水平，而 GF 处理后这些趋势被消除。circ_0059665 沉默抑制低氧环境下 NSCLC 细胞的增殖、侵袭和 M2 巨噬细胞极化，而过表达 NOV A2 则拮抗这一作用。此外，NOVA2 过表达逆转了 GF 对低氧处理 NSCLC 细胞的抑制作用。此外，GF 通过抑制 circ_0059665 抑制体内 NSCLC 肿瘤生长。
GF 处理在低氧环境下通过 circ_0059665/miR-512-5p/NOVA2 轴抑制 NSCLC 细胞的增殖、侵袭和 M2 巨噬细胞极化。
