The transition of cancer cells from epithelial state to mesenchymal state awarded hepatocellular carcinoma (HCC) stem cell properties and induced tumorigenicity, drug resistance, and high recurrence rate. Reversing the mesenchymal state to epithelial state by inducing mesenchymal-epithelial remodeling could inhibit the progression of HCC. Using high-throughput screening, chrysin was selected from natural products to reverse epithelial-mesenchymal transition (EMT) by selectively increasing CDH1 expression. The target identification suggested chrysin exerted its anti-HCC effect through covalently and specifically binding threonine 205 (Thr205) of alpha-enolase (ENO1). For the first time, we revealed that ENO1 bound β-catenin mRNA, and recruited YTHDF2 to identify the m6A modified β-catenin in the 3'-UTR region to degrade β-catenin mRNA. Eventually, the CDH1 gene expression was improved through the regulation of β-catenin mRNA. ENO1/β-catenin mRNA interaction might be a promising target for cellular plasticity reprogramming. Moreover, chrysin could mediate mesenchymal‒epithelial remodeling through increasing degradation of β-catenin mRNA by promoting the binding of ENO1 and β-catenin mRNA. To the best of our knowledge, chrysin is the first reported small molecule inducing β-catenin mRNA degradation through binding to ENO1. The water-soluble derivative of chrysin may be a natural product-derived lead compound for circumventing metastasis, recurrence, and drug resistance of HCC by mediating mesenchymal‒epithelial remodeling.

The PIF7 gene is a member of the bHLH family, playing a pivotal role in plant germination. However, its roles in tea plants (Camellia sinensis) remain largely unexplored. In this study, we cloned the phytochrome-interacting factor gene CsPIF7 to elucidate its role in the germination of tea plants. Subcellular localization analysis demonstrated that CsPIF7 was localized in the nucleus. Yeast one-hybrid and dual-luciferase reporter assays demonstrated that CsPIF7 directly bound to a specific region (7-321 bp) of the CsEXP promoter, thereby repressing the expression of CsEXP. These findings suggest that CsPIF7 may modulate the germination of tea plants by inhibiting the expression of CsEXP. Quantitative real-time PCR results showed that both CsPIF7 and CsEXP exhibited high expression levels in tea buds, with different expression patterns in response to abscisic acid (ABA) treatment. Furthermore, both CsPIF7 and CsEXP were upregulated under cold stress at 4 ℃, indicating their involvement in the cold response of tea plants. Taken together, these results suggest that CsPIF7 regulates CsEXP expression in an ABA-dependent manner, thereby influencing the germination of tea plants. This study provides both theoretical and experimental insights into the molecular mechanisms governing the germination of tea plants, laying the groundwork for further exploring the role of PIF7 in plant development and stress responses.
Camellia sinensis/metabolism* ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Abscisic Acid/pharmacology* ; Germination/genetics* ; Basic Helix-Loop-Helix Transcription Factors/metabolism* ; Promoter Regions, Genetic ; Cold Temperature