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Archive > Volume 32 Issue 7 > 2025,32(7):698-705. DOI:10.3872/j.issn.1007-385X.2025.07.004 Prev Next
Basic Research
2', 4'-dihydroxychalcone inhibits the proliferation and migration of colorectal cancer cells by regulating miR-7-5p-induced autophagy
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Abstract:
[Abstract] Objective: To investigate the molecular mechanism by which 2', 4'-dihydroxychalcone (D2) inhibits proliferation, migration, and epithelial-mesenchymal transition (EMT) in colorectal cancer cells through miR-7-5p-mediated autophagy. Methods: Human colorectal cancer cell lines HCT-15 and SW620 were treated with D2 at concentrations of 0, 12.5, 25, and 50 μmol/L. Cell proliferation and clonogenic capacity were evaluated using MTT and colony formation assays. Cell migration was assessed by wound healing and Transwell assays. WB assay was used to detect the expression of EMT-related proteins, autophagy-related proteins, and key components of the PI3K/AKT/mTOR pathway. Autophagosome formation was visualized by immunofluorescence staining. TCGA database and KEGG pathway analyses were performed to evaluate miR-7-5p expression and its association with colorectal cancer. RT-qPCR was used to quantify miR-7-5p expression, and lentiviral transduction was employed to establish stable miR-7-5p knockdown or overexpression cell lines. Results: D2 significantly inhibited colorectal cancer cell proliferation, migration, and EMT (P < 0.05 or P < 0.01). TCGA and KEGG analyses revealed that miR-7-5p expression was downregulated in colorectal cancer and closely associated with disease progression. D2 treatment (12.5, 25, and 50 μmol/L) significantly upregulated miR-7-5p expression in HCT-15 and SW620 cells (P < 0.01). At 25 μmol/L, D2 increased the expression of autophagy-related proteins (LC3 and p-ULK1) and inhibited the PI3K/ AKT/mTOR signaling pathway (P < 0.05), accompanied by increased autophagosome formation (P < 0.01). In miR-7-5p-knockdown cells treated with D2, the levels of LC3 and p-ULK1 were significantly reduced compared to D2-only treated cells (P < 0.05 or P < 0.01). Conclusion: D2 upregulates miR-7-5p to induce autophagy, thereby inhibiting colorectal cancer cell proliferation, migration, and EMT, possibly through suppression of the PI3K/AKT/mTOR signaling pathway.
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