Colorectal cancer (CRC) is a common malignancy with significant prevalence and mortality rates. Circular RNA FOXO3 (circ‑FOXO3; hsa_circ_0006404) has been reported to be involved in cancer regulation; however, its role in CRC is yet to be fully elucidated. Therefore, the aim of the present study was to investigate the effect of circ‑FOXO3 on CRC progression and identify its underlying mechanism. In the present study, the expression of circ‑FOXO3 was investigated in CRC tissues and cells via reverse transcription‑quantitative PCR. A Cell Counting Kit‑8 and colony formation assays were used to assess cell proliferation. The cell migratory and invasive abilities were detected using the Transwell migration and invasion assays. The luciferase assay and RNA pull‑down assay were conducted to verify the relationship of circ‑FOXO3, microRNA (miR)‑543 and Large tumor suppressor kinase 1 (LATS1). The results demonstrated that circ‑FOXO3 expression was downregulated in CRC tissues and cells, and was associated with poor overall survival of patients with CRC. Moreover, circ‑FOXO3 was associated with tumor size, distant metastasis, differentiation, lymph node metastasis and TMN stages of patients with CRC. circ‑FOXO3 overexpression suppressed CRC cell proliferation, migration and invasion. Luciferase assay and RNA pull‑down assay results indicated that circ‑FOXO3 functioned as a sponge for miR‑543. In addition, circ‑FOXO3 increased the expression of LATS1 via sponging miR‑543, thus inhibiting CRC cell aggressive features. Collectively, the present results suggested that circ‑FOXO3 inhibited CRC metastasis and progression via elevated LATS1 expression by sponging miR‑543. Therefore, circ‑FOXO3 may be a promising target for CRC therapy.

中文翻译：

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通过调节 miR-543/LATS1 轴鉴定环状 RNA-FOXO3 在结直肠癌中的肿瘤抑制作用。

结直肠癌 (CRC) 是一种常见的恶性肿瘤，具有显着的患病率和死亡率。据报道，环状 RNA FOXO3（circ-FOXO3；hsa_circ_0006404）参与癌症调节；然而，其在 CRC 中的作用尚未完全阐明。因此，本研究的目的是研究 circ-FOXO3 对 CRC 进展的影响并确定其潜在机制。在本研究中，通过逆转录-定量 PCR 研究了 circ-FOXO3 在 CRC 组织和细胞中的表达。Cell Counting Kit-8 和集落形成分析用于评估细胞增殖。使用 Transwell 迁移和侵袭试验检测细胞迁移和侵袭能力。进行荧光素酶测定和 RNA pull-down 测定以验证 circ-FOXO3、microRNA (miR)-543 和大肿瘤抑制激酶 1 (LATS1)。结果表明，circ-FOXO3 表达在 CRC 组织和细胞中下调，并且与 CRC 患者的总体生存率较差有关。此外，circ-FOXO3与CRC患者的肿瘤大小、远处转移、分化、淋巴结转移和TMN分期相关。circ-FOXO3 过表达抑制 CRC 细胞增殖、迁移和侵袭。荧光素酶测定和 RNA 下拉测定结果表明 circ-FOXO3 充当 miR-543 的海绵。此外，circ-FOXO3 通过海绵 miR-543 增加 LATS1 的表达，从而抑制 CRC 细胞的侵袭性特征。总的来说，目前的结果表明 circ-FOXO3 通过海绵 miR-543 提高 LATS1 表达来抑制 CRC 转移和进展。