title: Large intergenic non-coding RNA-ROR reverses gemcitabine-induced autophagy and apoptosis in breast cancer cells.
abstract: The purpose of this study was to elucidate the potential role of long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR) in gemcitabine (Gem)-induced autophagy and apoptosis in breast cancer cells. MDA-MB-231 cells were treated with short hairpin RNA (shRNA) to knockdown Linc-ROR expression in the presence of Gem. Gem treatment alone decreased cell survival and increased both apoptosis and autophagy. Gem treatment also increased the expression of LC3-II, Beclin 1, NOTCH1 and Bcl-2, but decreased expression of p62 and p53. Untreated MDA-MB-231 cell lines strongly expressed linc-ROR, but linc-ROR knockdown decreased cell viability and expression of p62 and p53 while increasing apoptosis. Linc-ROR knockdown also increased LC3-II/β-actin, Beclin 1, NOTCH1, and Bcl-2 expression, as well as the number of autophagic vesicles in MDA-MB-231 cells. Linc-ROR negatively regulated miR-34a expression by inhibiting histone H3 acetylation in the miR-34a promoter. We conclude that linc-ROR suppresses Gem-induced autophagy and apoptosis in breast cancer cells by silencing miR-34a expression.
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou 310000, P.R. China.
authors.forename: Yao-Min
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou 310000, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou 310000, P.R. China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Wei
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou 310000, P.R. China.
authors.forename: Ke-Zhen
authors.initials: KZ
authors.lastname: Lv
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou 310000, P.R. China.
authors.forename: Pei-Fen
authors.initials: PF
authors.lastname: Fu
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D006657:Histones; C000588825:Linc-RNA-RoR, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: breast cancer; gemcitabine; large intergenic non-coding; linc-ROR