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Archive > Volume 33 Issue 5 > 2026,33(5):537-544. DOI:10.3872/j.issn.1007-385X.2026.05.008 Prev Next
Basic Research
miR-433 inhibits cancer stem cell-like properties and enhances 5-FU sensitivity by targeting YAP1 in colorectal cancer HCT-116 cells
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Abstract:
[Abstract] Objective： To investigate the role of microRNA-433 (miR-433) in regulating stemness and chemoresistance in colorectal cancer (CRC) cells and to elucidate the underlying molecular regulatory mechanisms. Methods： A 5-FU?resistant HCT?116 cell line was established. The expression levels of miR-433 and stemness markers (SOX2, OCT4, and Nanog) were assessed using RT-qPCR and WB assay. The interaction between miR-433 and its target gene, YAP1, as well as the effect on the subcellular localization of YAP1, were verified through dual-luciferase reporter assays, immunofluorescence staining, and nuclear-cytoplasmic fractionation. Rescue experiments were conducted to confirm the functional role of the miR-433/YAP1 axis. The sensitivity of cells to 5-FU was evaluated using the CCK-8 assay. Results： Compared with parental cells, the expression of miR-433 was significantly downregulated in 5-FU- resistant HCT-116 cells (P < 0.05), whereas the expression of stemness markers (SOX2, OCT4, and Nanog) was upregulated (P < 0.05). Overexpression of miR-433 suppressed the expression of stemness markers, directly targeted YAP1, and inhibited the nuclear translocation of YAP1 (P < 0.05). Restoration of the expression of YAP1 partially reversed the inhibitory effect of miR-433 on stemness · · 537 中国肿瘤生物治疗杂志, 2026, 33(5) molecules (P < 0.05). Functionally, upregulation of miR-433 significantly enhanced the sensitivity of CRC cells to 5-FU; this effect was attenuated by the re-expression of YAP1 (P < 0.05). Conclusion： miR-433 suppresses the stem-like molecular phenotype of colorectal cancer cells and enhances sensitivity to chemotherapeutic agents by directly targeting the YAP1 pathway. The miR-433/YAP1 axis may serve as a potential novel therapeutic target for overcoming chemoresistance in CRC.
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