Upregulation of circ_0059961 suppresses cholangiocarcinoma development by modulating miR-629-5p/SFRP2 axis.

BACKGROUND

Cholangiocarcinoma (CCA) is a dangerous malignancy with a poor prognosis due to inefficient chemotherapy and surgery, and its pathophysiology could be linked to circular RNA (circRNAs) dysregulation. As a result, we wanted to see what role circ_0059961 plays in CCA.

METHODS

The quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_0059961, miR-629-5p, and secreted frizzled related protein 2 (SFRP2). Cell counting kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (Edu) assay were used to determine the role of circ_0059961 in proliferation. The MMP (Δψm) assay was used to assess cell apoptosis. Transwell assay was used to detect cell migration and invasion. The SFRP2 protein and epithelia-mesenchymal transition (EMT) process related proteins expression were measured using Western blot. The putative relationship between miR-629-5p and circ_0059961 or SFRP2 was validated by dual-luciferase reporter assay. The circ_0059961 roles in cholangiocarcinoma were also investigated by tumor xenograft assay.

RESULTS

Circ_0059961 expression was decreased in CCA tissues and carcinoma cells. Overexpressed circ_0059961 reduced tumor cell proliferation, migration, and invasion while inducing apoptosis. Circ_0059961 was proven to be a target of miR-629-5p, while miR-629-5p was confirmed to be a target of SFRP2. Circ_0059961 targeted miR-629-5p to modulate SFRP2 expression. Upregulation of miR-629-5p reversed the tumor-suppressive effects of circ_0059961 overexpression in rescue trials. Furthermore, SFRP2 overexpression restored miR-629-5p enrichment-promoted cell proliferation, migration, and invasion. Upregulated circ_0059961 reduced solid tumor growth in vivo.

CONCLUSION

Upregulation of circ_0059961 augmented SFRP2 expression by targeting miR-629-5p, which blocked cholangiocarcinoma tumor cell proliferation, migration, and invasion.