Browsing by Subject "miR-874-3p"

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    Circ-CCS regulates oxaliplatin resistance via targeting miR-874-3p/HK2 axis in colorectal cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Qiu, Xiaofeng; Xu, Qihua; Liao, Bingling; Hu, Sheng; Zhou, Ying; Zhang, Huijun
    Background. Colorectal cancer (CRC) is a malignancy that threatens the patient’s life. Previous reports showed that circular RNAs (circRNAs) can affect CRC development. Herein, we demonstrated the characters of circular RNA copper chaperone for superoxide dismutase (circ-CCS) in CRC tissues and cells. Methods. Circ-CCS, CCS mRNA, microRNA-8743p (miR-874-3p) and hexokinase 2 (HK2) were indicated by qRT-PCR and western blot in CRC. The cell roles were examined. Additionally, the interaction between miR-874-3p and circ-CCS or HK2 was forecasted by the bioinformatics method and assessed by dual-luciferase reporter assay. Finally, the mouse test was implemented to demonstrate the effect of circ-CCS in vivo. Results. Circ-CCS and HK2 were increased, whereas miR-874-3p was diminished in CRC. Circ-CCS lack subdued the IC50 value of oxaliplatin, cell proliferation, migration, invasion and glycolysis metabolism in CRC cells, while it endorsed cell apoptosis. Furthermore, miR-874-3p was validated as having a tumor repressive effect in CRC cells by restraining HK2. The results also showed that HK2 could regulate the development of CRC. In mechanism, circ-CCS targeted miR-874-3p to control HK2. In addition, circ-CCS knock-down also attenuated tumor growth in mice. Conclusion. Circ-CCS expedited CRC through miR874-3p/HK2
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    Knockdown of circ_0004585 enhances the chemosensitivity of colorectal cancer cells to 5-fluorouracil via the miR-874-3p/CCND1 axis
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wang, Shijie; Cao, Juan; Pei, Lijuan
    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.