PDF(Pubmed)
Abstract：
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.
摘要：
结直肠癌（CRC）是一种常见的恶性肿瘤，具有很高的患病率和死亡率。环状RNAFOXO3(circ‑FOXO3;hsa_circ_0006404)已被报道参与癌症调节;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。使用细胞计数试剂盒-8和集落形成测定来评估细胞增殖。使用Transwell迁移和侵袭测定法检测细胞迁移和侵袭能力。进行了荧光素酶测定和RNA下拉测定以验证circ‑FOXO3，microRNA（miR）‑543和大肿瘤抑制激酶1（LATS1）的关系。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相关。此外，circ-FOXO3与肿瘤大小有关，远处转移,分化,CRC患者的淋巴结转移和TMN分期。circ-FOXO3过表达抑制CRC细胞增殖，移民和入侵。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通过海绵作用miR‑543增加LATS1的表达，从而抑制CRC细胞侵袭性特征。总的来说，本研究结果提示circ‑FOXO3通过增强miR‑543,通过升高LATS1表达抑制CRC转移和进展.因此,circ-FOXO3可能是CRC治疗的一个有希望的靶点。
