title: Molecular signatures in response to Isoliquiritigenin in lymphoblastoid cell lines.
abstract: Isoliquiritigenin (ISL) has been known to induce cell cycle arrest and apoptosis of various cancer cells. However, genetic factors regulating ISL effects remain unclear. The aim of this study was to identify the molecular signatures involved in ISL-induced cell death of EBV-transformed lymphoblastoid cell lines (LCLs) using microarray analyses. For gene expression and microRNA (miRNA) microarray experiments, each of 12 LCL strains was independently treated with ISL or DMSO as a vehicle control for a day prior to total RNA extraction. ISL treatment inhibited cell proliferation of LCLs in a dose-dependent manner. Microarray analysis showed that ISL-treated LCLs represented gene expression changes in cell cycle and p53 signaling pathway, having a potential as regulators in LCL survival and sensitivity to ISL-induced cytotoxicity. In addition, 36 miRNAs including five miRNAs with unknown functions were differentially expressed in ISL-treated LCLs. The integrative analysis of miRNA and gene expression profiles revealed 12 putative mRNA-miRNA functional pairs. Among them, miR-1207-5p and miR-575 were negatively correlated with p53 pathway- and cell cycle-associated genes, respectively. In conclusion, our study suggests that miRNAs play an important role in ISL-induced cytotoxicity in LCLs by targeting signaling pathways including p53 pathway and cell cycle.
authors.affiliation: National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Republic of Korea.
authors.forename: Jae-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Hong
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Nam
authors.forename: Meeyul
authors.initials: M
authors.lastname: Hwang
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Bok-Ghee
authors.initials: BG
authors.lastname: Han
authors.forename: Jae-Pil
authors.initials: JP
authors.lastname: Jeon
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D047188:Chalcones / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D035683:MicroRNAs; C040920:isoliquiritigenin