title: Identification of microRNAs and mRNAs associated with multidrug resistance of human laryngeal cancer Hep-2 cells.
abstract: Multidrug resistance (MDR) poses a serious impediment to the success of chemotherapy for laryngeal cancer. To identify microRNAs and mRNAs associated with MDR of human laryngeal cancer Hep-2 cells, we developed a multidrug-resistant human laryngeal cancer subline, designated Hep-2/v, by exposing Hep-2 cells to stepwise increasing concentrations of vincristine (0.02-0.96'µM). Microarray assays were performed to compare the microRNA and mRNA expression profiles of Hep-2 and Hep-2/v cells. Compared to Hep-2 cells, Hep-2/v cells were more resistant to chemotherapy drugs (≈ 45-fold more resistant to vincristine, 5.1-fold more resistant to cisplatin, and 5.6-fold more resistant to 5-fluorouracil) and had a longer doubling time (42.33 ± 1.76 vs 28.75 ± 1.12'h, P<0.05), higher percentage of cells in G0/G1 phase (80.98 ± 0.52 vs 69.14 ± 0.89, P<0.05), increased efflux of rhodamine 123 (95.97 ± 0.56 vs 12.40 ± 0.44%, P<0.01), and up-regulated MDR1 expression. A total of 7 microRNAs and 605 mRNAs were differentially expressed between the two cell types. Of the differentially expressed mRNAs identified, regulator of G-protein signaling 10, high-temperature requirement protein A1, and nuclear protein 1 were found to be the putative targets of the differentially expressed microRNAs identified. These findings may open a new avenue for clarifying the mechanisms responsible for MDR in laryngeal cancer.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, The First Clinical Hospital, Norman Bethune College of Medicine, Jilin University, Changchun, China.
authors.forename: Wanzhong
authors.initials: W
authors.lastname: Yin
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Song
authors.forename: Xiangyan
authors.initials: X
authors.lastname: Cui
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology; D059585:G1 Phase Cell Cycle Checkpoints; D019450:Genes, MDR; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D035683:MicroRNAs / Q000302:isolation & purification*; D009363:Neoplasm Proteins / Q000235:genetics; D020710:RGS Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000302:isolation & purification*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020112:Rhodamine 123 / Q000493:pharmacokinetics; D012697:Serine Endopeptidases / Q000235:genetics; D046888:Tissue Array Analysis; D014750:Vincristine / Q000494:pharmacology
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D051792:Basic Helix-Loop-Helix Proteins; D002945:Cisplatin; D005472:Fluorouracil; D000074289:High-Temperature Requirement A Serine Peptidase 1; D035683:MicroRNAs; D009363:Neoplasm Proteins; D020710:RGS Proteins; D012333:RNA, Messenger; D020112:Rhodamine 123; D012697:Serine Endopeptidases; D014750:Vincristine; C513055:ABCB1 protein, human; C491643:NUPR1 protein, human; C101113:RGS10 protein, human; C474012:HTRA1 protein, human