Multi-omics reveals the anticancer mechanism of luteoloside on colorectal cancer in vivo and in vitro

Colorectal cancer (CRC) is a malignant tumor characterized by high incidence and fatality rates, ranking as the second most common cancer globally. Honeysuckle, a traditional medicinal plant, contains a large amount of the compound called luteoloside (LUS), which exhibits notable biological functions, particularly in cancer prevention and treatment. This study aimed to elucidate the anticancer mechanisms targeted by LUS, focusing on the interaction between miRNA and mRNA within the context of CRC pathogenesis. We assessed the impact of LUS on CRC using both in vivo and in vitro methods. The potential mechanisms of LUS on CRC HCT116 cells were further explored using immunohistochemistry, immunofluorescence, miRNA-seq and mRNA-seq, western blot, and qRT-PCR. The integrated analysis identified a total of 4519 DEGs and 30 DEMs that exhibited negative regulatory interactions, suggesting that LUS triggered both apoptosis and autophagy via endoplasmic reticulum (ER) stress and DNA damage-related pathways. 87 DEGs and 29 DEMs corresponding to protein processing in endoplasmic reticulum (PPER) and 36 DEGs and 23 DEMs corresponding to p53 pathways were identified via miRNA-target gene network analysis. Hub miRNAs and genes, including Hsa-miR-152-3p, hsa-mir-663a-p3, hsa-mir-663b-p3, mmu-miR-6240_R-5_1ss1CA, CANX and PPM1D were identified as central regulators of anticancer potential of LUS. These findings suggest miRNA-mediated central gene regulatory networks can serve as predictive models for molecular mechanisms of CRC, potentially offering new understanding into the pathogenesis of CRC, indicating that LUS has broad market prospects in the development and application of functional food, medicine and other fields.