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Transcription factor CCAAT/enhancer binding protein alpha up-regulates microRNA let-7a-1 in lung cancer cells by

Yani Lin1, Jian Zhao2, Xiaoyan Hu1

  • 1Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, 250012 People's Republic of China.

Cancer Cell International
|March 11, 2016
PubMed
Abstract

Insights

CCAAT/enhancer binding protein α (C/EBPα) down-regulation in lung cancer cells leads to decreased microRNA let-7a-1 expression. This study identifies let-7a-1 as a direct transcriptional target of C/EBPα in lung cancer.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • CCAAT/enhancer binding protein α (C/EBPα) and microRNA (miRNA) let-7a-1 are known tumor suppressors in various cancers, including lung cancer.
  • Dysregulation of C/EBPα and let-7a-1 is observed in lung cancer cells.

Purpose of the Study:

  • To investigate if let-7a-1 is a novel target of C/EBPα in lung cancer cells.
  • To elucidate the regulatory relationship between C/EBPα and let-7a-1 in lung cancer.

Main Methods:

  • Bioinformatic analysis of the let-7a-1 promoter for C/EBP binding sites.
  • Quantitative real-time PCR and Western blotting to assess gene and protein expression.
  • Dual-luciferase reporter gene assays to confirm transcriptional regulation.
  • Electrophoretic mobility shift assays and chromatin immunoprecipitation to validate C/EBPα binding to the let-7a-1 promoter.

Main Results:

  • C/EBPα and let-7a-1 were found to be downregulated in human lung cancer cell lines (A549, H1299).
  • C/EBPα was shown to increase let-7a-1 expression at the transcriptional level.
  • Four C/EBP binding elements in the let-7a-1 promoter were identified and confirmed to mediate C/EBPα's regulatory effect.

Conclusions:

  • Decreased levels of C/EBPα contribute to the downregulation of miRNA let-7a-1 in lung cancer cells.
  • let-7a-1 is a direct transcriptional target of C/EBPα, and this interaction is disrupted in lung cancer.
Keywords:
C/EBPαLung cancerPromoterlet-7a-1

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