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Journal of Cancer Research and Clinical Oncology

Published in:

01-11-2015 | Original Article – Cancer Research

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

Authors: Shufeng Li, Qiwei Wang, Qian Qiang, Haitao Shan, Minke Shi, Baojun Chen, Sheng Zhao, Liudi Yuan

Published in: Journal of Cancer Research and Clinical Oncology | Issue 11/2015

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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Title: Sp1-mediated transcriptional regulation of MALAT1 plays a critical role in tumor
Authors: Shufeng Li
Qiwei Wang
Qian Qiang
Haitao Shan
Minke Shi
Baojun Chen
Sheng Zhao
Liudi Yuan
Publication date: 01-11-2015
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 11/2015
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-015-1951-0

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Abstract

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