title: A novel long non-coding RNA lnc-GNAT1-1 is low expressed in colorectal cancer and acts as a tumor suppressor through regulating RKIP-NF-κB-Snail circuit.
abstract: The role of long non-coding RNAs (lncRNAs) in colorectal cancer (CRC) progression has not fully been elucidated. This study was designed to report the identification of a novel lncRNA, lnc-GNAT1-1, and its functional role in CRC progression.
  
  
  
  lncRNA expression profile microarray was performed in three paired primary and liver metastatic tissues of CRC, and a novel lncRNA, lnc-GNAT1-1, was identified to be a potential functional lncRNA. Quantitative real-time PCR was used to detect its expression in CRC tissues, cell lines, and patients' plasma, cell fractionation was used to evaluate its subcellular location. lnc-GNAT1-1 was knockdown by siRNA or overexpressed by a lentivirus vector, then in vitro an vivo experiments were performed to evaluate its biological role and the underlying mechanisms in CRC.
  
  
  
  Expression of lnc-GNAT1-1 was decreased in liver metastasis than the primary tumor, while the later one is lower than the paired normal mucosa. Decreased lnc-GNAT1-1 expression was associated unfavorable clinicopathological features and a poor prognosis of CRC patients. In multivariate analysis, lnc-GNAT1-1 was proved to be an independent prognostic factor. In plasma, lnc-GNAT1-1 was significant decreased in CRC patients than healthy donors, and with the TNM stages advanced, the plasma lnc-GNAT1-1 level decreased; Receiver operating characteristic curve (ROC curve) showed that plasma lnc-GNAT1-1 had a moderate to well diagnostic efficiency for CRC. In vitro experiments showed that knockdown of lnc-GNAT1-1 could inhibit the aggressive phenotypes of CRC cell lines. In vivo study showed that overexpression of lnc-GNAT1-1 could suppress the liver metastasis of CRC cells. Finally, we explored the underlying mechanism of the role lnc-GNAT1-1 plays in CRC, and found a positive correlation between lnc-GNAT1-1 and Raf kinase inhibitor protein (RKIP) expression both in cells and in patients' tissues. We further found that lnc-GNAT1-1 could regulate the RKIP-NF-κB-Snail circuit in CRC.
  
  
  
  We have demonstrated in this study that a novel lncRNA, lnc-GNAT1-1, is low expressed in colorectal cancer tissues and plasma, and acts as a tumor suppressor through regulating RKIP-NF-κB-Snail circuit.
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, People's Republic of China.|Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, 100044, People's Republic of China.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Ye
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, People's Republic of China. shenlong1977@163.com.|Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, 100044, People's Republic of China. shenlong1977@163.com.|Peking University People's Hospital, No. 11 Xizhimen South Street Xicheng District, Beijing, People's Republic of China. shenlong1977@163.com.
authors.forename: Zhanlong
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, People's Republic of China.|Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, 100044, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, People's Republic of China.|Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, 100044, People's Republic of China.
authors.forename: Yansen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, People's Republic of China.|Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, 100044, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, People's Republic of China.|Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, 100044, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, People's Republic of China.|Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, 100044, People's Republic of China.
authors.forename: Kewei
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, People's Republic of China. yeyingjiang@pkuph.edu.cn.|Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, 100044, People's Republic of China. yeyingjiang@pkuph.edu.cn.|Peking University People's Hospital, No. 11 Xizhimen South Street Xicheng District, Beijing, People's Republic of China. yeyingjiang@pkuph.edu.cn.
authors.forename: Yingjiang
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, People's Republic of China. shanwang60@sina.com.|Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, 100044, People's Republic of China. shanwang60@sina.com.|Peking University People's Hospital, No. 11 Xizhimen South Street Xicheng District, Beijing, People's Republic of China. shanwang60@sina.com.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics* / Q000556:secondary*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000235:genetics; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000097:blood / Q000235:genetics*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000235:genetics
chemical_list: D016328:NF-kappa B; C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D062085:RNA, Long Noncoding; D000071250:Snail Family Transcription Factors; C000625566:long non-coding RNA GNAT1-1, human
keywords: Long non-coding RNA; NF-κB; RKIP; Snail; lnc-GNAT1-1