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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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  1. Home
  2. Dnmt3a-mediated Dna Methylation And Transcription Inhibition Of Fzd5 Suppresses Lung Carcinogenesis.
  1. Home
  2. Dnmt3a-mediated Dna Methylation And Transcription Inhibition Of Fzd5 Suppresses Lung Carcinogenesis.

Related Experiment Video

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
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Published on: August 5, 2022

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DNMT3A-mediated DNA methylation and transcription inhibition of FZD5 suppresses lung carcinogenesis.

Jiqiao Shen1, Jinchen Su2, Xiangling Chu3

  • 1Department of Respiratory and Critical Care Medicine, Minhang Hospital, Fudan University, Shanghai, 201100, China.

Heliyon
|May 6, 2024

View abstract on PubMed

Summary
This summary is machine-generated.

Aberrant Frizzled 5 (FZD5) expression, driven by reduced DNA methylation, promotes non-small cell lung cancer (NSCLC) development. Restoring DNMT3A levels suppresses tumor growth and malignant cell behavior in NSCLC.

Keywords:
DNMT3AFZD5NSCLCUrethane

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Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Non-small cell lung cancer (NSCLC) is a major health concern.
  • Aberrant gene expression plays a critical role in NSCLC pathogenesis.
  • Frizzled 5 (FZD5) has been identified as a potential factor in NSCLC development.

Purpose of the Study:

  • To investigate the correlation between Frizzled 5 (FZD5) expression and non-small cell lung cancer (NSCLC).
  • To elucidate the role of FZD5 in NSCLC tumorigenesis and malignant behavior.
  • To explore the epigenetic regulation of FZD5 in NSCLC.

Main Methods:

  • Established a mouse model for primary NSCLC using urethane injection.
  • Utilized lentivirus-mediated FZD5 silencing in vivo and in vitro.
  • Assessed DNA methylation levels using quantitative methylation-specific PCR.
  • Investigated DNA methyltransferases (DNMTs) binding to the FZD5 promoter via chromatin immunoprecipitation.
  • Overexpressed DNMT3A in mice and NSCLC cells to confirm its regulatory role.
  • Main Results:

    • Elevated FZD5 expression was observed in NSCLC.
    • FZD5 knockdown reduced tumor incidence in mice and inhibited proliferation, migration, and invasion of NSCLC cells in vitro.
    • Reduced promoter methylation of FZD5 correlated with its aberrant upregulation in NSCLC.
    • DNMT3A, a suppressor of FZD5 transcription, was underexpressed in NSCLC.
    • DNMT3A upregulation suppressed lung carcinogenesis and malignant phenotypes in NSCLC.

    Conclusions:

    • Reduced DNA methylation-induced activation of FZD5 is linked to NSCLC onset and progression.
    • DNMT3A acts as a tumor suppressor in NSCLC by downregulating FZD5.
    • Targeting FZD5 and DNMT3A may offer therapeutic strategies for NSCLC.