title: Gene and microRNA expression reveals sensitivity to paclitaxel in laryngeal cancer cell line.
abstract: Paclitaxel is a widely used chemotherapy drug for advanced laryngeal cancer patients. However, the fact that there are 20-40% of advanced laryngeal cancer patients do not response to paclitaxel makes it necessary to figure out potential biomarkers for paclitaxel sensitivity prediction. In this work, Hep2, a laryngeal cancer cell line, untreated or treated with lower dose of paclitaxel for 24 h, was applied to DNA microarray chips for gene and miR expression profile analysis. Expression of eight genes altered significantly following paclitaxel treatment, which was further validated by quantitative real-time PCR. Four up-regulated genes were ID2, BMP4, CCL4 and ACTG2, in which ID2 and BMP4 were implicated to be involved in several drugs sensitivity. While the down-regulated four genes, MAPK4, FASN, INSIG1 and SCD, were mainly linked to the endoplasmic reticulum and fatty acid biosynthesis, these two cell processes that are associated with drug sensitivity by increasing evidences. After paclitaxel treatment, expression of 49 miRs was significantly altered. Within these miRs, the most markedly expression-changed were miR-31-star, miR-1264, miR-3150b-5p and miR-210. While the miRs putatively modulated the mRNA expression of the most significantly expression-altered genes were miR-1264, miR-130a, miR-27b, miR-195, miR-1291, miR-214, miR-1277 and miR-1265, which were obtained by miR target prediction and miRNA target correlation. Collectively, our study might provide potential biomarkers for paclitaxel sensitivity prediction and drug resistance targets in laryngeal cancer patients.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Shanghai First People's Hospital affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Cheng-Zhi
authors.initials: CZ
authors.lastname: Xu
authors.forename: Jin
authors.initials: J
authors.lastname: Xie
authors.forename: Bin
authors.initials: B
authors.lastname: Jin
authors.forename: Xin-Wei
authors.initials: XW
authors.lastname: Chen
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Sun
authors.forename: Bao-Xing
authors.initials: BX
authors.lastname: Wang
authors.forename: Pin
authors.initials: P
authors.lastname: Dong
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020128:Inhibitory Concentration 50; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D035683:MicroRNAs; D017239:Paclitaxel
keywords: Laryngeal cancer; cell lines; gene expression profiles; miR expression profiles; paclitaxel