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2,3,5,4’-Tetrahydroxystilbene-2-O-b-D-Glucoside modulates CHEK2 and CCND1 alternative splicing to inhibit MCF-7 cells proliferation

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Traditional Medicine Research 2024年第1期9卷 33-46页

作者： Hui Shen You-Zhi Zhang Peng-Yu Wang Shuo Zhang Huan Pan Bei-Bei Liu Long-Sheng Xu Jian-Fen Shen Department of Central Laboratory The First Affiliated Hospital of Jiaxing UniversityJiaxing 314000China School of Pharmacy Xianning Medical CollegeHubei University of Science and TechnologyXianning 437100China Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province Xianning Medical CollegeHubei University of Science and TechnologyXianning 437100China

Background:In our previous study,we observed a synergistic effect of 2,3,5,4’-Tetrahydroxystilbene-2-O-b-D-glucoside combined with adriamycin to induce apoptosis in MCF-7 breast cancer ***,the underlying mechanisms of epigenetic modifications,such as alternative splicing,have not been *** this study,we aimed to investigate the mechanism by which THSG inhibits MCF-7 cell proliferation using full-length transcriptome ***:First,cell viability was examined using the methyl thiazolyl tetrazolium method and full-length transcriptome sequencing was performed to identify genes and *** Ontology and Kyoto Encyclopedia of Genes and Genomes were used to identify the principal pathways and targets of *** cytometry analysis of cell cycle distribution was ***,the analysis of alternative splicing and domains of the key proteins was *** polymerase chain reaction and western blotting were performed for ***:THSG showed significant cytotoxic activity in MCF-7 ***-length transcriptome sequencing revealed differential alternative splicing with 173 upregulated and 263 downregulated *** analysis identified distinct differential expression of genes(CHEK2-211 and CCND1-201)involved in the cell cycle in the THSG-treated ***,alternative splicing types of CHEK2(mutually exclusive exon)and CCND1(intron retention).We found that THSG downregulated mRNA expression,as confirmed by quantitative polymerase chain reaction ***,protein structural analysis revealed that THSG treatment led to the generation of CHK2-211,which was the result of a mutation in the amino acid residues(GLU-150,ASN-151)of the CHEK2 domain(VAL-150,GLY-151).and CyclinD1-201 were obtained when an amino acid(ASP-267)in the domain was lost in ***,molecular docking analysis demonstrated that the domains of key proteins could bind THSG more effectively,with no difference in

关键词： THSG breast cancer full-length transcriptome sequencing alternative splicing

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