title: Sp1-mediated transcriptional regulation of MALAT1 plays a critical role in tumor.
abstract: BACKGROUND
  MALAT1 was discovered as a prognostic marker for lung cancer metastasis and has been found upregulated in many types of tumor, but its transcriptional regulation mechanism in tumors remains unclear.
  
  
  METHODS
  A deletion analysis of MALAT1 promoter region was performed to find the cis elements that were critical for the transcriptional activation of MALAT1 gene. Reporter gene assays were employed to analyze the effect of Sp1 on the promoter activity of MALAT1 gene. The binding activity of Sp1 with the promoter of MALAT1 gene was examined by EMSA and ChIP assay. Effects of Sp1 on regulation of MALAT1 were analyzed by RNA interference in vitro and in vivo mouse model.
  
  
  RESULTS
  By means of luciferase assay, Sp1 was found to activate the promoter of the human MALAT1 gene. The binding of Sp1 to this region was also detected by electrophoretic mobility shift and chromatin immunoprecipitation assays. Sp1 knockdown also decreased the MALAT1 and inhibited A549 lung cancer cells' growth and invasion in vitro. Furthermore, knockdown of Sp1 also mimicked the inhibition of MALAT1 in A549 lung cancer cells' growth and metastasis in vivo.
  
  
  CONCLUSIONS
  Taken together, our data suggest that upregulation of MALAT1 was mediated by the transcription factor Sp1 in A549 lung cancer cells, and Sp1 could be therapeutic target for cancer.
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Department of Biochemistry and Molecular Biology, Medical School of Southeast University, Nanjing, 210009, China. shufengli@seu.edu.cn.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Li
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Department of Biochemistry and Molecular Biology, Medical School of Southeast University, Nanjing, 210009, China.
authors.forename: Qiwei
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Department of Biochemistry and Molecular Biology, Medical School of Southeast University, Nanjing, 210009, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Qiang
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Department of Biochemistry and Molecular Biology, Medical School of Southeast University, Nanjing, 210009, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Shan
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Minke
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Baojun
authors.initials: B
authors.lastname: Chen
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Department of Biochemistry and Molecular Biology, Medical School of Southeast University, Nanjing, 210009, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Department of Biochemistry and Molecular Biology, Medical School of Southeast University, Nanjing, 210009, China.
authors.forename: Liudi
authors.initials: L
authors.lastname: Yuan
mesh_terms: D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering; D017384:Sequence Deletion / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; C557041:MALAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human
keywords: MALAT1; Sp1; Transcription regulation; lnc RNA