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Sp1-mediated transcriptional regulation of MALAT1 plays a critical role in tumor

  • Original Article – Cancer Research
  • Published:
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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.

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Abbreviations

MALAT1:

Metastasis-associated lung adenocarcinoma transcript 1

EMSA:

Electrophoretic mobility shift assay

ChIP:

Chromatin immunoprecipitation assay

lnc RNA:

Long noncoding RNA

ncRNA:

Noncoding RNA

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Acknowledgments

This work was supported by Grant from the Chinese National Nature Science Foundation (31070706) and by the Fund from Nanjing Health Bureau (ykk10082).

Conflict of interest

The authors declared that they have no conflict of interest.

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    Authors and Affiliations

    1. 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

      Shufeng Li, Qiwei Wang, Qian Qiang, Haitao Shan, Sheng Zhao & Liudi Yuan

    2. Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

      Minke Shi & Baojun Chen

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    1. Shufeng Li
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    Correspondence to Shufeng Li.

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    Shufeng Li, Qiwei Wang and Qian Qiang have contributed equally to this work.

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    Li, S., Wang, Q., Qiang, Q. et al. Sp1-mediated transcriptional regulation of MALAT1 plays a critical role in tumor. J Cancer Res Clin Oncol 141, 1909–1920 (2015). https://doi.org/10.1007/s00432-015-1951-0

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    • DOI: https://doi.org/10.1007/s00432-015-1951-0

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