title: The long noncoding RNA-ROR promotes the resistance of radiotherapy for human colorectal cancer cells by targeting the p53/miR-145 pathway.
abstract: OBJECTIVE
  Long intergenic noncoding RNAs (lincRNAs) have critical roles in elevating efficacy of anticancer therapy and tumor progression. Recent studies show that Regulator of Reprogramming (ROR) is aberrantly expressed in several types of cancer, including colorectal cancer (CRC). Radiotherapy is considered as a standard preoperative treatment. However, a considerable number of CRCs are resistant to radiotherapy. In this study, we evaluated the role of lincRNA-ROR in radiotherapy for CRC and detected the underlying molecular mechanism.
  
  
  METHODS
  Real-time polymerase chain reaction was employed to quantify the expression level of lincRNA-ROR in different CRC cell lines and tissue samples. Cell viability and apoptosis assays were used to confirm the radiotherapy-mediated effects by lincRNA-ROR altered expression. The direct impact of lincRNA-ROR on the expression of p53/miR-145 by loss-of-function and gain-of-function strategy was also analyzed. A xenograft mouse model was used to evaluate the role of linc-ROR in CRC treatment.
  
  
  RESULTS
  We discovered that lincRNA-ROR was upregulated in CRC cell lines and tissue samples. We further showed that knockdown of lincRNA-ROR enhanced the sensitivity to radiotherapy for CRC by inhibiting cell viability and promoting apoptosis. Activity of the p53/miR-145 pathway may help explain the role of lincRNA-ROR for stress-induced regulation in CRC therapy. Combined specific knockdown of lincRNA-ROR and radiotherapy treatment in xenograft model resulted in a significant reduction in the tumor growth.
  
  
  CONCLUSIONS
  LincRNA-ROR decreases sensitivity to radiotherapy via the negative regulation of p53/miR-145 and may represent a potential target for the treatment of CRC.
authors.affiliation: Department of Cancer Molecular and Biology, Cancer Research Institute of Harbin Medical University, Harbin, China.|Department of Cancer Molecular and Biology, Cancer Research Institute of Heilongjiang Academy of Medical Sciences, Harbin, China.
authors.forename: Pengxiang
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Cancer Molecular and Biology, Cancer Research Institute of Harbin Medical University, Harbin, China.|Department of Cancer Molecular and Biology, Cancer Research Institute of Heilongjiang Academy of Medical Sciences, Harbin, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Cancer Molecular and Biology, Cancer Research Institute of Harbin Medical University, Harbin, China.|Department of Cancer Molecular and Biology, Cancer Research Institute of Heilongjiang Academy of Medical Sciences, Harbin, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: An
authors.affiliation: Department of Radiation Oncology, The Third Hospital of Harbin Medical University, Harbin, China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Gastrointestinal Surgery, The Third Hospital of Harbin Medical University, Harbin, China.
authors.forename: Gan
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Immunology, College of Basic Medical Science, Changchun, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jie
authors.affiliation: Department of Cancer Molecular and Biology, Cancer Research Institute of Harbin Medical University, Harbin, China.|Department of Cancer Molecular and Biology, Cancer Research Institute of Heilongjiang Academy of Medical Sciences, Harbin, China.|Department of Medical Oncology, The Third Hospital of Harbin Medical University, Harbin, China.
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D058990:Molecular Targeted Therapy; D009368:Neoplasm Transplantation; D062085:RNA, Long Noncoding / Q000502:physiology*; D022661:RNA, Untranslated / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D015854:Up-Regulation
chemical_list: C541010:MIRN145 microRNA, human; C543499:MIRN145a microRNA, mouse; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D016159:Tumor Suppressor Protein p53
keywords: colorectal cancer; combined treatment; lincRNA-ROR; p53/miR-145 pathway; radiotherapy