title: Decreased long noncoding RNA SPRY4-IT1 contributing to gastric cancer cell metastasis partly via affecting epithelial-mesenchymal transition.
abstract: BACKGROUND
  Long noncoding RNAs (lncRNAs) are emerging as key regulators governing fundamental biological processes, and their disorder expression involves in tumorigenesis. SPRY4-IT1 (SPRY4 intronic transcript 1), a lncRNA derived from an intron within SPRY4 gene, involves in multiple cancers development. However, the expression pattern and biological function of SPRY4-IT1 in gastric cancer is still not well documented. Hence, we carried out the present study to investigate the potential role of SPRY4-IT1 in gastric carcinogenesis.
  
  
  METHODS
  QRT-PCR was performed to detect the expression of SPRY4-IT1 in 61 pairs of gastric cancer samples. Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of SPRY4-IT1. The effect of SPRY4-IT1 on proliferation was evaluated by MTT and colony formation assays. Gastric cancer cells transfected with pCDNA-SPRY4-IT1 were injected into nude mice to study the effect of SPRY4-IT1 on tumorigenesis and metastasis in vivo. Protein levels of SPRY4-IT1 targets were determined by western blot or fluorescence immunohistochemistry. ChIP assays were performed to investigate the effect of DNMT1 on SPRY4-IT1 expression. Differences between groups were tested for significance using Student's t test (two-tailed).
  
  
  RESULTS
  SPRY4-IT1 expression is decreased in gastric cancer tissues and associated with larger tumor size, advanced pathological stage, deeper depth of invasion and lymphatic metastasis. Patients with lower SPRY4-IT1 expression had a relatively poor prognosis. DNA methylation may be a key factor in controlling the SPRY4-IT1 expression. Furthermore, SPRY4-IT1 contributed to gastric cancer cells metastasis might partly via regulating epithelial-mesenchymal transition (EMT) process.
  
  
  CONCLUSIONS
  Low expression of SPRY4-IT1 is involved in progression and metastasis of gastric cancer and may represent a novel biomarker of poor prognosis in patients with gastric cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China. 1115769204@qq.com.
authors.forename: Min
authors.initials: M
authors.lastname: Xie
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China. 957714486@qq.com.
authors.forename: Feng-qi
authors.initials: FQ
authors.lastname: Nie
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China. sunming@njmu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China. 1423594097@qq.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Xia
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China. 1727136487@qq.com.
authors.forename: Yan-wen
authors.initials: YW
authors.lastname: Liu
authors.affiliation: The First Clinical Medical College of Nanjing Medical University, Nanjing, People's Republic of China. 897852507@qq.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China. dewei@njmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: De
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China. liuxianghua@njmu.edu.cn.
authors.forename: Xiang-hua
authors.initials: XH
authors.lastname: Liu
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D062085:RNA, Long Noncoding; C000605823:long noncoding RNA SPRY4-IT1, human; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse