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Updated: Dec 21, 2025

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ATF3 Demethylation Promotes the Transcription of ARL4C, Which Acts as a Tumor Suppressor in Human Breast Cancer

Liqi Li1,2, Rong-Mao Sun1, Guo-Qin Jiang1

  • 1Department of Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, People's Republic of China.

Oncotargets and Therapy
|May 20, 2020
PubMed
Abstract

Insights

Activating transcription factor 3 (ATF3) and ADP-ribosylation factor like-4 (ARL4) are decreased in breast cancer. Their restoration inhibits tumor growth, suggesting the ATF3/ARL4C axis as a potential therapeutic target and diagnostic biomarker.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Breast cancer is a prevalent malignancy globally.
  • The roles of Activating Transcription Factor 3 (ATF3) and ADP-ribosylation Factor Like-4C (ARL4C) in breast cancer remain incompletely understood.

Purpose of the Study:

  • To investigate the expression and functional significance of ATF3 and ARL4C in human breast cancer.
  • To elucidate the regulatory mechanisms, including promoter binding and epigenetic modifications, governing ATF3 and ARL4C expression.
  • To assess the prognostic value of ATF3 and ARL4C in breast cancer patients.

Main Methods:

  • Quantitative real-time PCR, Western blotting, and immunohistochemistry were used to measure ATF3 and ARL4C expression in breast cancer tissues.
  • Functional assays evaluated the impact of ATF3 or ARL4C overexpression on cancer cell growth, migration, and invasion.
  • TCGA database analysis identified correlations between ATF3 and ARL4C.
  • ATF3 binding to the ARL4C promoter and the effects of DNA methylation were investigated.
  • A meta-analysis correlated ATF3/ARL4C expression with patient prognosis.

Main Results:

  • ATF3 and ARL4C expression levels were significantly decreased in breast cancer tissues at both mRNA and protein levels.
  • Overexpression of ATF3 or ARL4C suppressed breast cancer cell proliferation, migration, and invasion.
  • ATF3 expression positively correlated with ARL4C, and ATF3 directly bound to the ARL4C promoter.
  • Hypermethylation negatively regulated ATF3 expression, while demethylation enhanced it, subsequently promoting ARL4C transcription.
  • Meta-analysis revealed that low ATF3 and/or ARL4C expression correlated with poorer breast cancer prognoses.

Conclusions:

  • The ATF3/ARL4C axis plays a crucial role in breast cancer progression.
  • This axis represents a potential biomarker for breast cancer diagnosis and prognosis determination.
  • Targeting the ATF3/ARL4C pathway offers a promising therapeutic strategy for breast cancer treatment.
Keywords:
5ʹ-Aza-dCARL4CATF3breast cancermethylation

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