title: Linc-ROR confers gemcitabine resistance to pancreatic cancer cells via inducing autophagy and modulating the miR-124/PTBP1/PKM2 axis.
abstract: OBJECTIVE
  In this study, we investigated the regulation of linc-ROR on autophagy and gemcitabine resistance of pancreatic cancer cells and further studied the underlying involvement of the miR-124/PTBP1/PKM2 axis in this regulation.
  
  
  METHODS
  Pancreatic cancer cell lines PANC-1 and MIAPaCa-2 cells were used as in vitro model. Autophagy was assessed by western blot of LC3 I/II and observation GFP-LC3 puncta. Cell viability was examined using CCK-8 assay. Cell apoptosis was examined by flow cytometric analysis of Annexin V/PI staining. QRT-PCR, RNA fluorescence in situ hybridization and dual luciferase assay were used to study the expression and the binding between linc-ROR and miR-124.
  
  
  RESULTS
  Linc-ROR siRNA significantly sensitized PANC-1 and MIAPaCa-2 cells to gemcitabine, while linc-ROR overexpression significantly reduced the sensitivity. Linc-ROR knockdown reduced basal autophagy, while linc-ROR overexpression markedly increased basal autophagy in the cells. Linc-ROR siRNA showed similar effect as 3-MA on enhancing gemcitabine-induced cell apoptosis and also reduced PKM2 expression. MiR-124 overexpression restored PKM1 and reduced PKM2 levels in the cells. In addition, miR-124 mimics also alleviated autophagy in pancreatic cancer cells. Both miR-124 mimics and PKM2 siRNA enhanced gemcitabine-induced cell apoptosis. In both pancreatic cell lines and PADC tissues, linc-ROR is negatively correlated with miR-124 expression. In addition, dual luciferase assay verified two 8mer binding sites between miR-124 and linc-ROR.
  
  
  CONCLUSIONS
  Linc-ROR confers gemcitabine resistance to pancreatic cancer cells at least partly via inducing autophagy. There is a linc-ROR/miR-124/PTBP1/PKM2 axis involved in regulation of gemcitabine resistance in pancreatic cancer cells.
authors: Department of Surgical Oncology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China. chenggangli@outlook.com.
authors: Chenggang
authors: C
authors: Li
authors: Department of Surgical Oncology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.
authors: Zhiming
authors: Z
authors: Zhao
authors: Department of Surgical Oncology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.
authors: Zhipeng
authors: Z
authors: Zhou
authors: Department of Surgical Oncology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.
authors: Rong
authors: R
authors: Liu
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D002352:Carrier Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D035683:MicroRNAs / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D038941:Polypyrimidine Tract-Binding Protein / Q000502:physiology*; D062085:RNA, Long Noncoding / Q000502:physiology*; D013963:Thyroid Hormones / Q000502:physiology*; D000093542:Gemcitabine; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D003841:Deoxycytidine; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D008565:Membrane Proteins; D035683:MicroRNAs; D038941:Polypyrimidine Tract-Binding Protein; D062085:RNA, Long Noncoding; D013963:Thyroid Hormones; D000093542:Gemcitabine; D000097810:Thyroid Hormone-Binding Proteins; C000588825:Linc-RNA-RoR, human; C509207:MIRN124 microRNA, human; C450006:PTBP1 protein, human
keywords: Autophagy; Gemcitabine; Linc-ROR; MiR-124; PKM2; Pancreatic cancer