Identification of the tumor‑suppressive role of circular RNA‑FOXO3 in colorectal cancer via regulation of miR‑543/LATS1 axis.

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.