Publication: Knockdown of circ_0004585 enhances the chemosensitivity of colorectal cancer cells to 5-fluorouracil via the miR-874-3p/CCND1 axis
Authors
Wang, Shijie ; Cao, Juan ; Pei, Lijuan
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-18-502
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info:eu-repo/semantics/article
Description
Abstract
Background. Colorectal cancer (CRC) is a
serious threat to human health and is drug-resistant.
Circular RNA _0004585 (circ_0004585) has been shown
to be expressed in CRC, but whether it plays a role in
CRC with chemoresistance remains unknown.
Therefore, this study aimed to investigate the potential
role of circ_0004585 in CRC with 5-fluorouracil (5-FU)
resistance.
Methods. The expression of related genes was
detected by quantitative real-time polymerase chain
reaction (qRT-PCR), and the protein expressions of
cleaved caspase-3, cleaved caspase-9, and cyclin D1
(CCND1) were detected by western blot. Cell functions
were identified using CCK-8, colony formation, flow
cytometry, tube formation and transwell assays. The
putative relationships between miR-874-3p and
circ_0004585 or CCND1 were validated by dualluciferase reporter assays. Animal experiments were
conducted to verify the effect of circ_0004585 on 5-FU
resistance in vivo.
Results. Circ_0004585 was highly expressed in CRC
tissues and cells, particularly in 5-FU-resistant CRC
tissues and cells. Circ_0004585 knockdown enhanced 5-
FU sensitivity to further inhibit CRC cell viability,
colony formation, cell migration and invasion, and
accelerate cell apoptosis. MiR-874-3p was the target of
circ_0004585, and miR-874-3p depletion partially
recovered the malignant behaviors of 5-FU-resistant
CRC cells that were blocked by silencing of
circ_0004585. In addition, CCND1 was the target of
miR-874-3p, and overexpression of CCND1 was able to
restore the malignant effects of 5-FU-resistant CRC cells
that were repressed by miR-874-3p enrichment. Animal
experiments confirmed that circ_0004585 knockdown
inhibited the growth of CRC tumors and enhanced 5-FU
sensitivity in vivo.
Conclusion. Circ_0004585 promotes the
development of CRC and increases 5-FU resistance in
CRC through the miR-874-3p/CCND1 axis. These
results suggest that circ_0004585 may be a therapeutic
target for 5-FU-ressitant CRC.
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