Background Lung adenocarcinoma (LUAD), a widespread histopathological subtype of lung cancer, is deemed as a malignant tumor with a peak risk of mortality. Emerged as RNA with a loop structure that depleted protein coding ability, circular RNA (circRNA) has been identified as a regulator in cancer progression. Circ-SOX4, identified as a novel circRNA, has not been studied in any cancer yet. Thus, the regulatory function that circ-SOX4 exerts on LUAD development remains obscure. Aim of the study This study aimed to investigate the biological function and molecular mechanism of circ-SOX4 in LUAD. Methods The expression of circ-SOX4 was detected by qRT-PCR. CCK-8, colony formation, transwell and wound healing assays were performed to explore the biological function of circ-SOX4 in LUAD. The interaction between miR-1270 and circ-SOX41 (or PLAGL2) was confirmed by RNA pull down, luciferase reporter and RIP assays. Results Circ-SOX4 was found to be obviously upregulated in LUAD tissues and cells, and knockdown of it inhibited cell proliferation, invasion and migration in LUAD. Furthermore, silenced circ-SOX4 also inhibited LUAD tumor growth. Molecular mechanism assays revealed that circ-SOX4 interacted with miR-1270 in LUAD. Besides, PLAGL2 was confirmed as a downstream gene of miR-1270. Rescue assays validated that miR-1270 suppression or PLAGL2 overexpression countervailed circ-SOX4 depletion-mediated inhibition on cell proliferation, invasion and migration in LUAD. Additionally, it was discovered that circ-SOX4/miR-1270/PLAGL2 axis activated WNT signaling pathway in LUAD. Conclusions Circ-SOX4 boosted the development of LUAD and activate WNT signaling pathway through sponging miR-1270 and modulating PLAGL2, which provided a valuable theoretical basis for exploring underlying therapeutic target in LUAD.

中文翻译：

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Circ-SOX4 通过海绵化 miR-1270 和调节 PLAGL2 激活 WNT 信号通路来驱动肺腺癌的发生和发展。

背景肺腺癌（LUAD）是一种广泛存在的肺癌组织病理学亚型，被认为是一种死亡率最高的恶性肿瘤。作为具有耗尽蛋白质编码能力的环状结构的RNA出现，环状RNA（circRNA）已被确定为癌症进展的调节剂。Circ-SOX4 被鉴定为一种新型 circRNA，尚未在任何癌症中进行研究。因此，circ-SOX4 对 LUAD 发育的调节功能仍然不清楚。研究目的本研究旨在探讨circ-SOX4在LUAD中的生物学功能和分子机制。方法采用qRT-PCR检测circ-SOX4的表达。进行 CCK-8、集落形成、transwell 和伤口愈合测定以探索 circ-SOX4 在 LUAD 中的生物学功能。miR-1270 和 circ-SOX41（或 PLAGL2）之间的相互作用通过 RNA pull down、荧光素酶报告基因和 RIP 分析得到证实。结果发现Circ-SOX4在LUAD组织和细胞中明显上调，敲除后抑制了LUAD中细胞的增殖、侵袭和迁移。此外，沉默的 circ-SOX4 也抑制了 LUAD 肿瘤的生长。分子机制分析表明，circ-SOX4 与 LUAD 中的 miR-1270 相互作用。此外，PLAGL2被证实为miR-1270的下游基因。救援试验证实 miR-1270 抑制或 PLAGL2 过表达抵消了 circ-SOX4 耗竭介导的对 LUAD 中细胞增殖、侵袭和迁移的抑制。此外，还发现 circ-SOX4/miR-1270/PLAGL2 轴激活了 LUAD 中的 WNT 信号通路。